This document outlines the syllabus for a Medical Genetics course at the Islamic University of Gaza. It includes:
- A list of chapter topics to be covered over the semester, including introduction to genetics and genomics in medicine, principles of clinical cytogenetics, patterns of inheritance, and cancer genetics.
- Information about exams, assignments, and grading. The midterm exam will be 30% and the final exam will be 60% of the overall grade.
- An overview of the first chapter, introducing medical genetics and genomic medicine. It discusses applying genetics to medical practice, gene mapping, molecular causes of disease, and genetic counseling.
- Details about clinical cytogenetics techniques like karyotyping
Presentation1.pptx, imaging of genetic diseases. (3)Abdellah Nazeer
This document summarizes different types of genetic diseases including their classification, inheritance patterns, and examples. It discusses disorders caused by mutations in single genes including autosomal dominant, autosomal recessive, and X-linked conditions. Specific genetic diseases are explained such as neurofibromatosis, cystic fibrosis, and lysosomal storage disorders. The document also covers disorders associated with defects in enzymes, structural proteins, receptors, and genes that regulate cell growth.
Molecular cytogenetics involves combining molecular biology techniques with cytogenetics. This document discusses several molecular cytogenetic techniques including karyotyping, FISH, CGH, and SKY. Karyotyping allows visualization of whole chromosome sets but cannot detect small structural abnormalities. FISH uses fluorescent probes to detect specific DNA sequences on chromosomes. CGH analyzes copy number variations by comparing test and reference DNA samples hybridized to probes. SKY simultaneously visualizes all chromosome pairs in different colors, making abnormalities easy to identify. These techniques are useful for detecting chromosomal abnormalities that can cause genetic disorders and economic losses if spread within animal populations. Preventing the dissemination of abnormalities through genetic testing is important.
The karyotype shows a deletion of the long arm of chromosome 5 and an extra copy of chromosome 9. Deletions and extra copies of chromosomes are common abnormalities in chronic lymphocytic leukemia (CLL) that help determine prognosis. Deletion of the long arm of chromosome 5 is seen in a subset of CLL patients and is associated with poor prognosis.
Mitochondrial DNA (mtDNA) encodes proteins that are essential components of the oxidative phosphorylation (OXPHOS) system located in the inner mitochondrial membrane. Defects in mtDNA or nuclear genes involved in mitochondrial functions can cause a wide range of mitochondrial diseases. MtDNA is maternally inherited and mutations can be transmitted from mother to offspring. Common mitochondrial diseases include Chronic Progressive External Ophthalmoplegia (CPEO), Kearns-Sayre Syndrome (KSS), MELAS, MERRF, and Leber Hereditary Optic Neuropathy (LHON). These diseases have varying clinical features depending on the mutation and often affect the brain, muscles, and eyes.
This document discusses several single-gene disorders including cystic fibrosis, sickle cell anemia, fragile X syndrome, Huntington's disease, and muscular dystrophy. It provides details on the genetics, symptoms, inheritance patterns, and impact of each disorder. References are also included at the end related to catastrophic antiphospholipid syndrome.
This document discusses single gene disorders and their patterns of inheritance. It begins by defining some key genetic terms like genes, alleles, loci, genotypes, phenotypes, mutations, and codons. It then describes the main patterns of inheritance for single gene disorders: autosomal dominant, autosomal recessive, X-linked recessive, and X-linked dominant. For each pattern, it explains how the disorder is transmitted from parents to children based on whether the gene is located on an autosome or sex chromosome, and if the trait is dominant or recessive. The document provides examples like sickle cell anemia, cystic fibrosis, and Tay-Sachs disease to illustrate different types of mutations and their effects. It concludes by
Chromosomal breakage syndromes are conditions caused by improper DNA repair that lead to genomic instability. They include Louis-Bar syndrome, Fanconi anemia, Bloom syndrome, and Xeroderma pigmentosum. These syndromes are caused by mutations in genes responsible for DNA repair, resulting in an increased risk of cancer due to a failure to repair DNA damage. Common symptoms include bone marrow failure, skin abnormalities like dark spots, neurological issues, and premature aging. Management focuses on protecting skin from sun exposure and treating associated health problems.
This document discusses cytogenetics and chromosome analysis techniques. It begins with an introduction to human chromosomes and chromosomal abnormalities. It then describes various types of chromosomal mutations and abnormalities that can be detected through karyotyping and fluorescence in situ hybridization (FISH). The document provides detailed procedures for chromosome sample preparation from bone marrow and blood cultures, as well as staining and analysis techniques like Giemsa staining and G-banding. The importance of chromosomal studies for diagnosing conditions like Turner syndrome and Klinefelter syndrome is also highlighted.
Presentation1.pptx, imaging of genetic diseases. (3)Abdellah Nazeer
This document summarizes different types of genetic diseases including their classification, inheritance patterns, and examples. It discusses disorders caused by mutations in single genes including autosomal dominant, autosomal recessive, and X-linked conditions. Specific genetic diseases are explained such as neurofibromatosis, cystic fibrosis, and lysosomal storage disorders. The document also covers disorders associated with defects in enzymes, structural proteins, receptors, and genes that regulate cell growth.
Molecular cytogenetics involves combining molecular biology techniques with cytogenetics. This document discusses several molecular cytogenetic techniques including karyotyping, FISH, CGH, and SKY. Karyotyping allows visualization of whole chromosome sets but cannot detect small structural abnormalities. FISH uses fluorescent probes to detect specific DNA sequences on chromosomes. CGH analyzes copy number variations by comparing test and reference DNA samples hybridized to probes. SKY simultaneously visualizes all chromosome pairs in different colors, making abnormalities easy to identify. These techniques are useful for detecting chromosomal abnormalities that can cause genetic disorders and economic losses if spread within animal populations. Preventing the dissemination of abnormalities through genetic testing is important.
The karyotype shows a deletion of the long arm of chromosome 5 and an extra copy of chromosome 9. Deletions and extra copies of chromosomes are common abnormalities in chronic lymphocytic leukemia (CLL) that help determine prognosis. Deletion of the long arm of chromosome 5 is seen in a subset of CLL patients and is associated with poor prognosis.
Mitochondrial DNA (mtDNA) encodes proteins that are essential components of the oxidative phosphorylation (OXPHOS) system located in the inner mitochondrial membrane. Defects in mtDNA or nuclear genes involved in mitochondrial functions can cause a wide range of mitochondrial diseases. MtDNA is maternally inherited and mutations can be transmitted from mother to offspring. Common mitochondrial diseases include Chronic Progressive External Ophthalmoplegia (CPEO), Kearns-Sayre Syndrome (KSS), MELAS, MERRF, and Leber Hereditary Optic Neuropathy (LHON). These diseases have varying clinical features depending on the mutation and often affect the brain, muscles, and eyes.
This document discusses several single-gene disorders including cystic fibrosis, sickle cell anemia, fragile X syndrome, Huntington's disease, and muscular dystrophy. It provides details on the genetics, symptoms, inheritance patterns, and impact of each disorder. References are also included at the end related to catastrophic antiphospholipid syndrome.
This document discusses single gene disorders and their patterns of inheritance. It begins by defining some key genetic terms like genes, alleles, loci, genotypes, phenotypes, mutations, and codons. It then describes the main patterns of inheritance for single gene disorders: autosomal dominant, autosomal recessive, X-linked recessive, and X-linked dominant. For each pattern, it explains how the disorder is transmitted from parents to children based on whether the gene is located on an autosome or sex chromosome, and if the trait is dominant or recessive. The document provides examples like sickle cell anemia, cystic fibrosis, and Tay-Sachs disease to illustrate different types of mutations and their effects. It concludes by
Chromosomal breakage syndromes are conditions caused by improper DNA repair that lead to genomic instability. They include Louis-Bar syndrome, Fanconi anemia, Bloom syndrome, and Xeroderma pigmentosum. These syndromes are caused by mutations in genes responsible for DNA repair, resulting in an increased risk of cancer due to a failure to repair DNA damage. Common symptoms include bone marrow failure, skin abnormalities like dark spots, neurological issues, and premature aging. Management focuses on protecting skin from sun exposure and treating associated health problems.
This document discusses cytogenetics and chromosome analysis techniques. It begins with an introduction to human chromosomes and chromosomal abnormalities. It then describes various types of chromosomal mutations and abnormalities that can be detected through karyotyping and fluorescence in situ hybridization (FISH). The document provides detailed procedures for chromosome sample preparation from bone marrow and blood cultures, as well as staining and analysis techniques like Giemsa staining and G-banding. The importance of chromosomal studies for diagnosing conditions like Turner syndrome and Klinefelter syndrome is also highlighted.
A mitochondrion (singular of mitochondria) is part of every cell in the body that contains genetic material.
Mitochondria are responsible for processing oxygen and converting substances from the foods we eat into energy for essential cell functions.
The mitochondria of the zygote come from the oocyte, that is, from the mother and almost never from the sperm, form of transmission is called maternal inheritance
Which mitochondrial gene is mutated.
The extent of replicative segregation of the mutant mitochondrial genome during the early stages of embryonic development.
The abundance of the mutant mitochondrial gene in a particular tissue.
The threshold level of mutant mitochondrial DNA required in a tissue before an abnormality is evident clinically
Mitochondrial disease affects tissues most highly dependent on ATP production
*Nerves
*Muscles
Endocrine
Kidney
Low energy-requiring tissues are rarely directly affected, but may be secondarily
Lung
Connective tissue
Symptoms can be intermittent
Increased energy demand (illness, exercise)
Decreased energy supply (fasting)
Common feature
myoclonus epilepsy, deafness, blindness, anemia, diabetes, seizures and loss of cerebral blood supply (stroke).
Myoclonic epilepsy and ragged-red fiber disease (MERRF)
MERRF is a member of a group of disorders called mitochondrial encephalomyopathies that feature mitochondrial defects with altered brain and muscle functions.
The term “ragged red fibers” refers to large clumps of abnormal mitochondria that accumulate mostly in muscle cells and are stained red by a dye that is specific for complex II of the electron transport chain.
rare, maternally inherited, heteroplasmic, (point mutation in tRNA lysine gene)
Mutation is MTTK*MERRF8344G.
MT means mitochondrial gene is mutated
T means transfer RNA gene
K means the single-letter amino acid designation for lysine
MERRF means the clinical features
8344G means the mutant nucleotide is guanine (G) at nucleotide position 8344
If 90% of the mitochondria in nerve and muscle cells carry the MTTK*MERRF8344G mutation, then the defining symptoms of MERRF are present.
Maternally inherited mitochondrial disease
The MTTL1*MELAS3243G mutation accounts for more than 80% of the cases of MELAS.
This base substitution is in one of the two mitochondrial transfer RNALeu genes.
the A3243G mutation occurs in thetRNALeu(UUR) gene
When this mutation is present in ≥90% of the mitochondrial DNA of muscle tissue, there is an increased likelihood of recurrent strokes, dementia, epilepsy, and ataxia.
When heteroplasmy for the A3243G mutation
is ~40% to 50%, chronic progressive external ophthalmoplegia (CPEO), myopathy, and deafness are likely to occur.
Other MELAS mutations occur at sites 3252, 3271, and 3291 within the tRNALeu(UUR) gene and in the mitochondrial tRNAVal (MTTV) and COX III (MTCO3) genes.
Reduced activities in Complexes I and IV are established
Fragile X syndrome is a genetic disorder caused by a mutation on the X chromosome involving expansion of the CGG repeat region in the FMR1 gene. This results in reduced or absent FMRP protein which is important for neural development. Symptoms can include intellectual disabilities, autism-like behaviors, large testes in males, and physical features like prominent ears and flat feet. It is typically diagnosed through genetic testing. While there is no cure, early intervention including therapies can help maximize learning and development.
The document discusses cytogenetics, which involves the study of chromosomes through cell culture and karyotyping. Chromosomes can be analyzed for their number and structure to detect abnormalities. Specific staining techniques like Q-, G-, R-, and C-banding produce distinct banding patterns that allow identification of each chromosome type. Karyotyping involves organizing chromosomes based on these patterns to detect any abnormalities associated with diseases.
This document discusses human genetic disorders. It begins with an introduction to genes and genetics. It then defines genetic disorders as diseases caused by abnormalities in DNA, including point mutations or changes to entire chromosomes. The document outlines the history of genetics research. It describes several types of genetic disorders including single gene, multifactorial, chromosomal, and mitochondrial disorders. Specific genetic disorders are then discussed as examples, including galactosemia, Alzheimer's disease, sickle cell anemia, Huntington's disease, and Down syndrome. The document concludes with some references used in its preparation.
Here, Genetic disorder and chromosomal abnormality discussed briefly. *Types of the genetic disorder *briefly discussed on different genetic diseases *chromosomal anomaly i.e. structural and numerical anomaly. etc.
Karyotyping is a medical test that examines chromosomes in a cell sample. It is performed to count chromosomes, identify structural changes, determine sex, diagnose genetic disorders, and find chromosomal causes of birth defects or disabilities. The test involves growing cells in culture, treating them with chemicals, taking photos of the chromosomes under a microscope, and creating a karyotype image showing the complete set of chromosomes. Attention is paid to characteristics like length, centromere position, and banding pattern. Karyotyping can reveal chromosomal changes like aneuploidy, where one or more entire chromosomes are added or deleted, or structural changes such as deletions, duplications, inversions, or translocations of chromosome segments.
This document discusses the increasing use of genetics in clinical medicine. It covers topics like germline alterations, genetic susceptibility to common diseases, the role of primary care physicians in genetics, and advances in genetic testing techniques. The importance of understanding a patient's family history and genetic risks is emphasized. Different patterns of genetic inheritance for various conditions are reviewed, along with examples of monogenic disorders and cancer syndromes. Emerging areas like pharmacogenomics and personalized medicine are also mentioned.
Genetic disorders can be caused by mutations to genes or chromosomes. Gene defects affect a single gene, usually impacting one protein, while chromosomal defects impact many genes on a chromosome. Genetic disorders are inherited in autosomal dominant, autosomal recessive, or sex-linked patterns. Examples provided include cystic fibrosis (recessive), Huntington's disease (dominant), and hemophilia (sex-linked). Chromosomal defects like monosomy, trisomy, and translocations can be detected via karyotyping, which identifies abnormalities involving number or structure of chromosomes. Specific conditions discussed are Turner syndrome, Down syndrome, and Klinefelter syndrome.
Chromosomes are cellular structures that carry genes. They are composed of DNA and protein and are found in the nucleus of cells. Genetic information is contained in the linear sequence of DNA bases on chromosomes. There are normally 46 chromosomes in humans arranged into 22 paired autosomes and two sex chromosomes. Chromosomal abnormalities can be numerical, involving extra or missing chromosomes, or structural, involving changes in chromosome structure like deletions, translocations, or inversions. Karyotyping allows visualization of chromosomes and identification of any abnormalities.
The document discusses different patterns of inheritance for single gene disorders:
- Autosomal dominant disorders are expressed when only one copy of the abnormal gene is present and there is a 50% chance of passing it to offspring. Examples include Huntington's disease.
- Autosomal recessive disorders require two copies of the abnormal gene to be expressed and carriers can be unaffected. Examples include many inborn errors of metabolism.
- X-linked disorders are sex-linked, with recessive disorders mostly affecting males and dominant disorders affecting females. Examples include G6PD deficiency and vitamin D-resistant rickets.
Chromosomal breakage syndromes are a group of rare, inherited disorders characterized by defects in DNA repair that lead to increased cancer risk. The major types discussed were ataxia telangiectasia, Fanconi anemia, Bloom syndrome, and xeroderma pigmentosum. These syndromes are caused by mutations that disrupt critical DNA repair pathways, leading to genomic instability and improper DNA repair. Common features include cancer predisposition, developmental defects, and skin abnormalities like pigmentation changes. Diagnosis involves genetic testing, cytogenetic analysis of chromosome breaks and rearrangements, and assessing clinical manifestations.
This document contains a series of slides explaining autosomal dominant inheritance from parents to children. The slides show that autosomal dominant conditions are caused by alterations in genes located on chromosomes other than the sex chromosomes. If one parent has the altered gene and passes it on to their child, the child has a 50% chance of inheriting the condition. An example is provided of a family where raised cholesterol is inherited in this autosomal dominant pattern. The slides are intended to demonstrate autosomal dominant inheritance for teaching purposes.
Gaucher disease is an inherited disorder caused by a deficiency of the glucocerebrosidase enzyme, which causes harmful substances to accumulate in organs. There are several types of Gaucher disease. Type 1 is the most common and usually does not affect the nervous system. Types 2 and 3 do affect the nervous system and can cause neurological problems. Symptoms vary depending on type but may include bone and organ enlargement, fatigue, easy bruising, and lung and heart problems. Diagnosis involves blood tests, imaging, and genetic testing. Treatment options include enzyme replacement therapy and bone marrow transplant for severe cases.
Genes play a significant role in determining risk of developing type 2 diabetes. Having one or both parents with the condition increases risk by 15-75%, while identical twins show a 90% concordance rate. Several genes have been identified that may contribute to diabetes through effects on insulin secretion, action, fat metabolism and storage. However, environmental factors like diet and lifestyle are also important, as adoption of a Western lifestyle can increase risk even in populations that were previously low-risk. Both genes and environment interact to promote conditions like insulin resistance through their combined effects on cells and metabolism.
20150918 C.Izzi - 22q11.2 Microdeletion Syndrome: Understanding the Emerging...Roberto Scarafia
22q11.2 Microdeletion Syndrome:
Understanding the Emerging
Importance of this Syndrome
Dr.ssa Claudia Izzi
Centro di Diagnosi Prenatale
Dipartimento Ostetrico-Ginecologico
Azienda Spedali Civili di Brescia
This document discusses various topics in human genetics including:
1. It defines human genetics as the scientific study of human variation and heredity, and medical genetics as the study of the hereditary nature of human disease.
2. Genetic diseases can be caused by inherited mutations, chromosomal abnormalities, or mutations in somatic cells (cancer). Inherited diseases can be due to nuclear or mitochondrial genetic mutations.
3. Examples of inherited genetic disorders and their inheritance patterns are discussed, including autosomal dominant disorders like achondroplasia and autosomal recessive disorders like thalassemia.
Multifactorial disorders are caused by multiple genes interacting with environmental factors, with each factor making a small contribution. Common multifactorial disorders include asthma, autoimmune diseases, cancers, cardiovascular diseases, diabetes, and mood disorders. The risk of developing a multifactorial disorder is influenced by family history and other genetic and environmental risk factors. Treatment depends on the specific disorder but may include controlling environmental triggers, medication, and lifestyle changes.
The document provides information on various mitochondrial disorders including Kearns-Sayre syndrome, MELAS syndrome, and Mitochondrial Neurogastrointestinal Encephalopathy Syndrome (MNGIE). It describes the symptoms, causes, and diagnosis of each disorder. Kearns-Sayre syndrome is characterized by progressive paralysis of the eye muscles and can affect multiple systems. MELAS syndrome causes seizures, headaches, and muscle weakness and is caused by mitochondrial DNA mutations. MNGIE is a rare multisystem disorder causing gastrointestinal problems and is caused by mutations in the TYMP gene encoding thymidine phosphorylase.
X inactivation is the process by which one of the two X chromosomes in female mammals is randomly inactivated. This occurs early in embryonic development through the expression of long non-coding Xist RNA from the future inactive X chromosome, which coats and silences that chromosome. Genes on the inactive X are transcriptionally silenced through epigenetic modifications, though some genes escape inactivation. The process ensures equal expression of X-linked genes between males and females through dosage compensation.
This document provides an overview of mitochondrial disorders including their characteristics, inheritance patterns, clinical presentations, diagnostic process, and treatment approaches. Mitochondrial disorders are caused by dysfunction of the mitochondrial respiratory chain and can affect multiple organ systems. Diagnosis involves considering the patient's history, symptoms, family history, laboratory and imaging testing, and potentially muscle biopsy. While there is no proven effective treatment, symptomatic management and supportive therapies like exercise, respiratory chain cofactors, antioxidants, and correcting secondary deficits may help address certain aspects of these complex, multi-system disorders.
6 clinical cytogenetics-disorders of the autosomes and the sex chromosomesAli Qatrawi
This document discusses Down syndrome (trisomy 21), including its prevalence, characteristic physical features, developmental effects, underlying genetic causes and variations, recurrence risks, and clinical management. Some key points include:
- Down syndrome is caused by trisomy of chromosome 21 and affects approximately 1 in 800 live births.
- It is characterized by developmental delays, distinctive facial features, and increased risk of health issues such as heart defects.
- Nearly all cases are due to errors in meiotic cell division, with around 90% originating from the mother's eggs and risk increasing with maternal age.
- The recurrence risk after one pregnancy affected is low at around 1%, but is higher for translocation or mosaic cases.
This seminar presentation discusses genetics and human affairs. It begins with introductions and definitions of key genetic terms like chromosomes, genes, alleles, nucleotides and codons. It then covers topics like human genome project, genetic diseases and their patterns of inheritance, chromosomal abnormalities, gene therapy, and concludes that genetics provides insight into human traits and health.
A mitochondrion (singular of mitochondria) is part of every cell in the body that contains genetic material.
Mitochondria are responsible for processing oxygen and converting substances from the foods we eat into energy for essential cell functions.
The mitochondria of the zygote come from the oocyte, that is, from the mother and almost never from the sperm, form of transmission is called maternal inheritance
Which mitochondrial gene is mutated.
The extent of replicative segregation of the mutant mitochondrial genome during the early stages of embryonic development.
The abundance of the mutant mitochondrial gene in a particular tissue.
The threshold level of mutant mitochondrial DNA required in a tissue before an abnormality is evident clinically
Mitochondrial disease affects tissues most highly dependent on ATP production
*Nerves
*Muscles
Endocrine
Kidney
Low energy-requiring tissues are rarely directly affected, but may be secondarily
Lung
Connective tissue
Symptoms can be intermittent
Increased energy demand (illness, exercise)
Decreased energy supply (fasting)
Common feature
myoclonus epilepsy, deafness, blindness, anemia, diabetes, seizures and loss of cerebral blood supply (stroke).
Myoclonic epilepsy and ragged-red fiber disease (MERRF)
MERRF is a member of a group of disorders called mitochondrial encephalomyopathies that feature mitochondrial defects with altered brain and muscle functions.
The term “ragged red fibers” refers to large clumps of abnormal mitochondria that accumulate mostly in muscle cells and are stained red by a dye that is specific for complex II of the electron transport chain.
rare, maternally inherited, heteroplasmic, (point mutation in tRNA lysine gene)
Mutation is MTTK*MERRF8344G.
MT means mitochondrial gene is mutated
T means transfer RNA gene
K means the single-letter amino acid designation for lysine
MERRF means the clinical features
8344G means the mutant nucleotide is guanine (G) at nucleotide position 8344
If 90% of the mitochondria in nerve and muscle cells carry the MTTK*MERRF8344G mutation, then the defining symptoms of MERRF are present.
Maternally inherited mitochondrial disease
The MTTL1*MELAS3243G mutation accounts for more than 80% of the cases of MELAS.
This base substitution is in one of the two mitochondrial transfer RNALeu genes.
the A3243G mutation occurs in thetRNALeu(UUR) gene
When this mutation is present in ≥90% of the mitochondrial DNA of muscle tissue, there is an increased likelihood of recurrent strokes, dementia, epilepsy, and ataxia.
When heteroplasmy for the A3243G mutation
is ~40% to 50%, chronic progressive external ophthalmoplegia (CPEO), myopathy, and deafness are likely to occur.
Other MELAS mutations occur at sites 3252, 3271, and 3291 within the tRNALeu(UUR) gene and in the mitochondrial tRNAVal (MTTV) and COX III (MTCO3) genes.
Reduced activities in Complexes I and IV are established
Fragile X syndrome is a genetic disorder caused by a mutation on the X chromosome involving expansion of the CGG repeat region in the FMR1 gene. This results in reduced or absent FMRP protein which is important for neural development. Symptoms can include intellectual disabilities, autism-like behaviors, large testes in males, and physical features like prominent ears and flat feet. It is typically diagnosed through genetic testing. While there is no cure, early intervention including therapies can help maximize learning and development.
The document discusses cytogenetics, which involves the study of chromosomes through cell culture and karyotyping. Chromosomes can be analyzed for their number and structure to detect abnormalities. Specific staining techniques like Q-, G-, R-, and C-banding produce distinct banding patterns that allow identification of each chromosome type. Karyotyping involves organizing chromosomes based on these patterns to detect any abnormalities associated with diseases.
This document discusses human genetic disorders. It begins with an introduction to genes and genetics. It then defines genetic disorders as diseases caused by abnormalities in DNA, including point mutations or changes to entire chromosomes. The document outlines the history of genetics research. It describes several types of genetic disorders including single gene, multifactorial, chromosomal, and mitochondrial disorders. Specific genetic disorders are then discussed as examples, including galactosemia, Alzheimer's disease, sickle cell anemia, Huntington's disease, and Down syndrome. The document concludes with some references used in its preparation.
Here, Genetic disorder and chromosomal abnormality discussed briefly. *Types of the genetic disorder *briefly discussed on different genetic diseases *chromosomal anomaly i.e. structural and numerical anomaly. etc.
Karyotyping is a medical test that examines chromosomes in a cell sample. It is performed to count chromosomes, identify structural changes, determine sex, diagnose genetic disorders, and find chromosomal causes of birth defects or disabilities. The test involves growing cells in culture, treating them with chemicals, taking photos of the chromosomes under a microscope, and creating a karyotype image showing the complete set of chromosomes. Attention is paid to characteristics like length, centromere position, and banding pattern. Karyotyping can reveal chromosomal changes like aneuploidy, where one or more entire chromosomes are added or deleted, or structural changes such as deletions, duplications, inversions, or translocations of chromosome segments.
This document discusses the increasing use of genetics in clinical medicine. It covers topics like germline alterations, genetic susceptibility to common diseases, the role of primary care physicians in genetics, and advances in genetic testing techniques. The importance of understanding a patient's family history and genetic risks is emphasized. Different patterns of genetic inheritance for various conditions are reviewed, along with examples of monogenic disorders and cancer syndromes. Emerging areas like pharmacogenomics and personalized medicine are also mentioned.
Genetic disorders can be caused by mutations to genes or chromosomes. Gene defects affect a single gene, usually impacting one protein, while chromosomal defects impact many genes on a chromosome. Genetic disorders are inherited in autosomal dominant, autosomal recessive, or sex-linked patterns. Examples provided include cystic fibrosis (recessive), Huntington's disease (dominant), and hemophilia (sex-linked). Chromosomal defects like monosomy, trisomy, and translocations can be detected via karyotyping, which identifies abnormalities involving number or structure of chromosomes. Specific conditions discussed are Turner syndrome, Down syndrome, and Klinefelter syndrome.
Chromosomes are cellular structures that carry genes. They are composed of DNA and protein and are found in the nucleus of cells. Genetic information is contained in the linear sequence of DNA bases on chromosomes. There are normally 46 chromosomes in humans arranged into 22 paired autosomes and two sex chromosomes. Chromosomal abnormalities can be numerical, involving extra or missing chromosomes, or structural, involving changes in chromosome structure like deletions, translocations, or inversions. Karyotyping allows visualization of chromosomes and identification of any abnormalities.
The document discusses different patterns of inheritance for single gene disorders:
- Autosomal dominant disorders are expressed when only one copy of the abnormal gene is present and there is a 50% chance of passing it to offspring. Examples include Huntington's disease.
- Autosomal recessive disorders require two copies of the abnormal gene to be expressed and carriers can be unaffected. Examples include many inborn errors of metabolism.
- X-linked disorders are sex-linked, with recessive disorders mostly affecting males and dominant disorders affecting females. Examples include G6PD deficiency and vitamin D-resistant rickets.
Chromosomal breakage syndromes are a group of rare, inherited disorders characterized by defects in DNA repair that lead to increased cancer risk. The major types discussed were ataxia telangiectasia, Fanconi anemia, Bloom syndrome, and xeroderma pigmentosum. These syndromes are caused by mutations that disrupt critical DNA repair pathways, leading to genomic instability and improper DNA repair. Common features include cancer predisposition, developmental defects, and skin abnormalities like pigmentation changes. Diagnosis involves genetic testing, cytogenetic analysis of chromosome breaks and rearrangements, and assessing clinical manifestations.
This document contains a series of slides explaining autosomal dominant inheritance from parents to children. The slides show that autosomal dominant conditions are caused by alterations in genes located on chromosomes other than the sex chromosomes. If one parent has the altered gene and passes it on to their child, the child has a 50% chance of inheriting the condition. An example is provided of a family where raised cholesterol is inherited in this autosomal dominant pattern. The slides are intended to demonstrate autosomal dominant inheritance for teaching purposes.
Gaucher disease is an inherited disorder caused by a deficiency of the glucocerebrosidase enzyme, which causes harmful substances to accumulate in organs. There are several types of Gaucher disease. Type 1 is the most common and usually does not affect the nervous system. Types 2 and 3 do affect the nervous system and can cause neurological problems. Symptoms vary depending on type but may include bone and organ enlargement, fatigue, easy bruising, and lung and heart problems. Diagnosis involves blood tests, imaging, and genetic testing. Treatment options include enzyme replacement therapy and bone marrow transplant for severe cases.
Genes play a significant role in determining risk of developing type 2 diabetes. Having one or both parents with the condition increases risk by 15-75%, while identical twins show a 90% concordance rate. Several genes have been identified that may contribute to diabetes through effects on insulin secretion, action, fat metabolism and storage. However, environmental factors like diet and lifestyle are also important, as adoption of a Western lifestyle can increase risk even in populations that were previously low-risk. Both genes and environment interact to promote conditions like insulin resistance through their combined effects on cells and metabolism.
20150918 C.Izzi - 22q11.2 Microdeletion Syndrome: Understanding the Emerging...Roberto Scarafia
22q11.2 Microdeletion Syndrome:
Understanding the Emerging
Importance of this Syndrome
Dr.ssa Claudia Izzi
Centro di Diagnosi Prenatale
Dipartimento Ostetrico-Ginecologico
Azienda Spedali Civili di Brescia
This document discusses various topics in human genetics including:
1. It defines human genetics as the scientific study of human variation and heredity, and medical genetics as the study of the hereditary nature of human disease.
2. Genetic diseases can be caused by inherited mutations, chromosomal abnormalities, or mutations in somatic cells (cancer). Inherited diseases can be due to nuclear or mitochondrial genetic mutations.
3. Examples of inherited genetic disorders and their inheritance patterns are discussed, including autosomal dominant disorders like achondroplasia and autosomal recessive disorders like thalassemia.
Multifactorial disorders are caused by multiple genes interacting with environmental factors, with each factor making a small contribution. Common multifactorial disorders include asthma, autoimmune diseases, cancers, cardiovascular diseases, diabetes, and mood disorders. The risk of developing a multifactorial disorder is influenced by family history and other genetic and environmental risk factors. Treatment depends on the specific disorder but may include controlling environmental triggers, medication, and lifestyle changes.
The document provides information on various mitochondrial disorders including Kearns-Sayre syndrome, MELAS syndrome, and Mitochondrial Neurogastrointestinal Encephalopathy Syndrome (MNGIE). It describes the symptoms, causes, and diagnosis of each disorder. Kearns-Sayre syndrome is characterized by progressive paralysis of the eye muscles and can affect multiple systems. MELAS syndrome causes seizures, headaches, and muscle weakness and is caused by mitochondrial DNA mutations. MNGIE is a rare multisystem disorder causing gastrointestinal problems and is caused by mutations in the TYMP gene encoding thymidine phosphorylase.
X inactivation is the process by which one of the two X chromosomes in female mammals is randomly inactivated. This occurs early in embryonic development through the expression of long non-coding Xist RNA from the future inactive X chromosome, which coats and silences that chromosome. Genes on the inactive X are transcriptionally silenced through epigenetic modifications, though some genes escape inactivation. The process ensures equal expression of X-linked genes between males and females through dosage compensation.
This document provides an overview of mitochondrial disorders including their characteristics, inheritance patterns, clinical presentations, diagnostic process, and treatment approaches. Mitochondrial disorders are caused by dysfunction of the mitochondrial respiratory chain and can affect multiple organ systems. Diagnosis involves considering the patient's history, symptoms, family history, laboratory and imaging testing, and potentially muscle biopsy. While there is no proven effective treatment, symptomatic management and supportive therapies like exercise, respiratory chain cofactors, antioxidants, and correcting secondary deficits may help address certain aspects of these complex, multi-system disorders.
6 clinical cytogenetics-disorders of the autosomes and the sex chromosomesAli Qatrawi
This document discusses Down syndrome (trisomy 21), including its prevalence, characteristic physical features, developmental effects, underlying genetic causes and variations, recurrence risks, and clinical management. Some key points include:
- Down syndrome is caused by trisomy of chromosome 21 and affects approximately 1 in 800 live births.
- It is characterized by developmental delays, distinctive facial features, and increased risk of health issues such as heart defects.
- Nearly all cases are due to errors in meiotic cell division, with around 90% originating from the mother's eggs and risk increasing with maternal age.
- The recurrence risk after one pregnancy affected is low at around 1%, but is higher for translocation or mosaic cases.
This seminar presentation discusses genetics and human affairs. It begins with introductions and definitions of key genetic terms like chromosomes, genes, alleles, nucleotides and codons. It then covers topics like human genome project, genetic diseases and their patterns of inheritance, chromosomal abnormalities, gene therapy, and concludes that genetics provides insight into human traits and health.
Genetics and periodontal disease
Patients with periodontitis show inflammatory destruction of the supporting tissues around the teeth. Loss of connective tissue and collagen in the gingiva is characteristic, along with loss of periodontal ligament and resorption of alveolar bone. Thus the tooth roots become exposed to the oral environment, and the root and root cementum are colonized with a bacterial biofilm, which can calcify to form dental calculus. The chronicity and mostly slow progression of this disease results in tooth mobility, loss of chewing function, esthetic disturbances and, ultimately, if left untreated, tooth exfoliation. Moreover, periodontal inflammation has systemic effects; it can induce low grade systemic inflammation, which has negative effects on other organs.
Periodontitis is a complex chronic inflammatory disease with nonlinear progression that is caused by various factors each playing a role simultaneously and interacting with each other. The various factors determine the immune fitness of a subject. The host exists in a symbiotic relationship with the oral microbiome to maintain homeostasis. Loss of homeostasis results from loss of the host balance and an aberrant host response. This aberrant host response can manifest as a hyper‐ or hyporesponsiveness and/or lack of sufficient resolution of inflammatory reactions. The consequent chronic inflammation elicits changes in the ecology of the subgingival environment providing favorable conditions for the overgrowth of pathobionts that further propagate periodontal inflammation. The factors that determine immune fitness include: (a) genetic factors and epigenetic factors; (b) lifestyle factors; (c) comorbidities; (d) local or dental factors and factors that act randomly; and (e) pathobionts in a dysbiotic subgingival biofilm. Variants in at least 65 genes to date have been suggested as being associated with periodontitis based on genome‐wide association studies and candidate gene case control studies. Interestingly, reports have found pleiotropy between periodontitis and cardiovascular diseases. To date, 4 genetic loci are shared between coronary artery disease and periodontitis. The shared genes suggest that periodontitis is not causally related to atherosclerotic diseases, but rather both conditions are sequelae of similar (the same?) aberrant inflammatory pathways. In addition to variations in genomic sequences, epigenetic modifications of DNA can affect the genetic blueprint of the host responses.
The document discusses reproductive sequencing technology and next generation sequencing (NGS) to detect genetic diseases before embryo transfer. NGS can be used in preconception, preimplantation, prenatal and postnatal testing to avoid abnormal pregnancies. NGS can identify most major genetic disorders like aneuploidy. The rest of the document discusses the chromosomes individually, providing details on their size, number of genes, genetic disorders associated with abnormalities of each chromosome including trisomies, monosomies, and other structural abnormalities.
This is a lecture presented by Dr.Omer Yahia Describing the first step of in the Role of molecular diagnostics through out the life. Give a brief shading out on the procedures for sample collection and types of diseases and syndromes undergone such tests .
This document provides an outline for a chapter on genetics and heredity. It begins with an introduction to the topic and definitions of key terms such as DNA, genes, alleles, and genotypes. It then discusses medical genetics, including human chromosomes, Mendelian inheritance, modes of inheritance such as autosomal recessive and dominant traits as well as sex-linked inheritance. The document also covers chromosomal and genetic anomalies including mutations, aneuploidy involving extra or missing chromosomes, and structural anomalies involving breaks or deletions of chromosomes. It concludes with information on genetic testing and counseling.
Seminar 9- Genetic Approaches in the Study of Oral Disorders.pptxswarnimakhichi
This document discusses genetic approaches used in the study of oral disorders. It begins with an overview of genetics, including definitions and the history of genetics. It then covers basic genetic principles like chromosomes, genes, and DNA. It describes different types of genetic disorders like Mendelian inheritance patterns and chromosomal anomalies. It also discusses multifactorial inheritance and how common oral diseases have a genetic basis involving gene-environment interactions. The document outlines approaches to identifying genes associated with diseases, including single nucleotide polymorphisms and genome-wide association studies. It concludes with examples of Mendelian disorders related to oral health.
This document discusses genetics and genetic disorders. It begins by outlining the objectives of exploring how genetics has changed healthcare, describing expanded nursing roles in genetics counseling, and identifying commonly tested genetic disorders. It then defines genetics and genomics, explaining why studying genetics is important. Several terms used in genetics are defined, and different patterns of inheritance for genetic disorders are described, including multifactorial, unifactorial, autosomal dominant and recessive, and X-linked inheritance. Specific genetic disorders that follow each pattern are provided as examples. The document concludes by discussing chromosome abnormalities, including abnormalities of number and structure, and provides examples of several common chromosomal disorders.
The document summarizes a genetics course taught by Dr. Ahmed Elshebiny. The course covers basic principles of medical genetics including the structure of DNA and chromosomes. It examines the genetic basis of various diseases and inheritance patterns. The course also explores applications of genetics in clinical practice such as genetic testing and gene therapy.
This document provides an overview of genetics and heredity. It discusses DNA and chromosomes, how genes determine traits (phenotype) from our genetic code (genotype), how a single cell develops into a full organism through cell differentiation and gene interactions, and different patterns of inheritance such as dominant/recessive genes. It also covers genetic abnormalities like Down syndrome and how nature and nurture both influence traits and conditions over one's lifetime. Genetic counseling and testing are discussed as ways to learn about genetic risks but also have uncertainties.
This document provides an overview of genetics and genetic abnormalities relevant to hematology. It begins with definitions of key genetic terms. It then discusses chromosomal abnormalities associated with hematological conditions like hemoglobinopathies, leukemias, and bleeding disorders. Specific examples of genetic abnormalities are described, such as translocations in CML and AML. The document outlines various genetic tests used in hematology and stresses the importance of genetic studies in disease classification and management. It emphasizes the role of genetics in understanding inherited hematological diseases.
Clinical genetics is one of the most rapidly advancing fields in medicine. Spectacular progress has been achieved in this century with unravelling of the entire draft sequence of the human genome. A major contribution of these advances has been in diagnosis, management and prenatal diagnosis of genetic disorders as treatment in most cases is difficult or impossible and where available beyond the means of most families. Genetic technology is advancing rapidly, bringing new, safer and more sensitive ways to diagnose genetic conditions pre- and postnatally. These advances will bring about profound changes in the way we deliver obstetric services to women and their families. Diagnosing a genetic disorder not only allows for disease-specific management options but also has implications for the affected individual's entire family. Hence, a working understanding of the underlying concepts of genetic disease is important for all practicing clinicians. Although it is impossible to know all aspects of clinical and molecular genetics, basic knowledge of certain topics is a must for all practicing obstetrician/gynecologists.
The advances likes Next Generation Sequencing is more advanced than Microarray Compatability Genomic hybridization and it is 100% of sensitivity and specificity regarding aneuploidy sequencing from all biological samples.
The document discusses various genetic studies of schizophrenia, including family, twin, and adoption studies. Family studies found an increased risk of schizophrenia in relatives of schizophrenic probands, suggesting a genetic basis. Twin studies estimated the heritability of schizophrenia to be around 80%, while adoption studies found an increased risk of schizophrenia in children adopted away from schizophrenic biological mothers. Overall, these various study designs provide strong evidence for a genetic contribution to schizophrenia.
This document summarizes genetic factors associated with periodontitis. It discusses various genetic studies related to chronic and aggressive periodontitis, including studies on gene polymorphisms like IL1, TNF, FCγR, IL10, and others. It also covers genetic terminology, types of genetic studies like twin studies, family studies, case-control studies and genome-wide association studies. Specific gene mutations linked to syndromes associated with periodontitis are mentioned.
This document provides definitions for genetic terms and discusses the practical applications of genetics in nursing. It defines key terms like DNA, genes, alleles, and more. It then discusses how genetics knowledge helps nurses to understand disease basis, enable early diagnosis, contribute to health promotion, prevent genetic conditions, manage genetic care and counseling, provide referrals, and address social/ethical issues. Nurses need genetics training to identify, support, refer and care for people with genetic disorders or risk.
This document discusses medical genetics and the study of hereditary diseases. It covers several key topics:
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Dan Geschwind, MD, PhD: Advances in Genetics 2016Semel Admin
Advances in genetics have identified hundreds of genes associated with autism spectrum disorder (ASD) risk. Knowing the genetic causes has implications for treatment, recurrence risk, and prevention. While ASD has extreme genetic heterogeneity, studies in animal models, human cells, and post-mortem tissue aim to identify convergent biological pathways and circuits impacted across various genetic mutations. This research seeks to develop targeted therapies for ASD and demonstrates the potential of precision medicine approaches for neurodevelopmental disorders.
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Date: May 29, 2024
Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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Remote Sensing and Geographic Information Systems
9
Changes in vegetation cover refer to variations in the distribution, composition, and overall
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2. oNussbaum et al: Thompson & Thompson
Genetics in Medicine 7E
Medical Genetics (2012-2013)2
3. Medical Genetics (2012-2013)3
Chapter Topic
1 Introduction: Genetics And Genomics In Medicine
5 Principles of Clinical Cytogenetics
6
Clinical Cytogenetics: Disorders of the Autosomes and the Sex
Chromosomes
Midterm exam
7 Patterns of Single-Gene Inheritance
8 Genetics of Common Disorders with Complex Inheritance
9
Genetic Variation in Individuals and Populations: Mutation and
Polymorphism
16 Cancer Genetics and Genomics
Clinical Case Studies Illustrating Genetic Principles
Final exam
5. o Clinical Case studies illustrating genetic principles
o Pages: 231-321
o Will be assigned later during the course
o Topics illustrated by the instructor will be avoided
o A schedule will be determined starting after the
midterm exam
Medical Genetics (2012-2013)5
7. o Medical genetics involves any application of
genetics to medical practice
o Studies of the inheritance of diseases in families,
o Mapping of disease genes to specific locations on
chromosomes
o Analyses of the molecular mechanisms through which
genes cause disease
o Diagnosis and treatment of genetic disease
o Gene therapy
o Genetic counseling (risks, prognoses, and treatments to
patients and their families)
7 Medical Genetics (2012-2013)
8. oGenomic medicine seeks to apply a large-
scale analysis of the human genome to
improve medical care
oincluding the control of gene expression
ohuman gene variation
ointeractions between genes and the environment
8 Medical Genetics (2012-2013)
9. o Any disease is the result of the combined action of
genes and environment
o the relative role of the genetic component may be
large or small
o Three main types among disorders with genetic
factors:
o chromosome disorders
o single-gene disorders
o multifactorial disorders
9 Medical Genetics (2012-2013)
10. o Caused by an excess or a deficiency of the genes
contained in whole chromosomes or chromosome
segments.
o E.g. an extra copy of chromosome 21 Down
syndrome
o Common as a group
o affecting about 7 per 1000 liveborn infants
o accounting for about half of all spontaneous first-
trimester abortions
10 Medical Genetics (2012-2013)
11. o Caused by individual mutant genes
o One or both of a pair of chromosomes may be
affected
o In a few cases, affects the mitochondrial genome
o E.g. cystic fibrosis, sickle cell anemia, and Marfan
syndrome
o Individually, most are rare,
o 1 in 500 to 1000 individuals but is usually much less
o As a group are responsible for a significant
proportion of disease and death
11 Medical Genetics (2012-2013)
12. o A result of one, two, or more different genes
o together can predispose to a serious defect
o often in concert with environmental factors.
o All have a genetic contribution
o increased risk for recurrence in relatives of affected
individuals
o increased frequency in identical twins
o yet show inheritance patterns in families that do not fit
the characteristic patterns seen in single-gene defects.
o The majority of diseases
o 5% in the pediatric population
o more than 60% in the entire population
12 Medical Genetics (2012-2013)
13. 13
Some diseases (e.g., cystic fibrosis) are strongly
determined by genes, whereas others (e.g., infectious
diseases) are strongly determined by environment.
Medical Genetics (2012-2013)
14. o Eukaryotes have multiple linear chromosomes in a
number characteristic of the species
o Most have two versions of each chromosome, and so
are diploid (2N).
o Diploid cells are produced by haploid (N) gametes
that fuse to form a zygote.
o The zygote then undergoes development, forming a
new individual.
14 Medical Genetics (2012-2013)
15. o Chromosome pairs in
diploid organisms are
homologous chromosomes
o One member of each pair
(homolog) is inherited from
each parent.
o Chromosomes that have
different genes and do not
pair are nonhomologous
chromosomes
15 Medical Genetics (2012-2013)
16. o Animals and some plants have male and female
cells with distinct chromosome sets
o One sex has a matched pair (e.g., human females with
XX) and the other has an unmatched pair (human male
with XY)
o Autosomes are chromosomes other than sex
chromosomes.
16 Medical Genetics (2012-2013)
17. o Please read chapter 2 of the Textbook,
o From Cell cycle (page:13) to the end of chapter (page
23)
o Ask me for any inquiry
o The first exam will include questions from topics of
the chapter
Medical Genetics (2012-2013)17
19. 19
oThe study of chromosomes
oTheir structure
oTheir inheritance
oApplied to the practice of medical genetics
oChromosome disorders:
oAbnormalities as a result of microscopically
visible changes in chromosome number or
structure
oA number of clinical conditions (genetic disease)
oReproductive wastage
oCongenital malformation
oMental retardation
oPathogenesis of cancer
19 Medical Genetics (2012-2013)
20. o Responsible for hundreds of identifiable
syndromes
o Collectively more common than single-gene
disorders
o In nearly 1% of all live births
o In about 2% of pregnancies in women older than 35
who undergo prenatal diagnosis
o In fully half of all spontaneous first-trimester abortions
20 Medical Genetics (2012-2013)
21. o Examination of chromosomes
o General morphology and organization
o Molecular and genomic composition
o Used for routine clinical purpose:
o May be performed on WBCs, skin biopsy, fibroblasts,
tumor biopsies
2121 Medical Genetics (2012-2013)
22. Medical Genetics (2012-2013)22
• WBC obtained
from peripheral
blood are
cultured
• WBCs are
stimulated to
divide and then
arrested in
metaphase with
chemicals
• Hypotonic
solutions are used
to release
chromosomes
• Chromosomes are fixed
and stained by one of
several techniques
• Chromosomes are analyzed
24. 24
o Problems of early growth and development:
o failure to thrive, developmental delay, dysmorphic
faces, multiple malformations, short stature, ambiguous
genitalia and mental retardation.
o Most frequent in, but not restricted to children with no
definite non-chromosomal diagnosis
o Stillbirth and neonatal death
o About 10% of stillbirth and neonatal death
o Fertility problems:
o women presenting with amenorrhea
o History of infertility or recurrent miscarriage
24 Medical Genetics (2012-2013)
25. 25
o Family history:
o a known or suspected chromosomal abnormality in a
first degree relative
o Neoplasia
o all cancers are associated with one or more
chromosomal abnormality
o Pregnancy in a woman of advanced age (>35
yrs)
25 Medical Genetics (2012-2013)
26. 26
o By a number of specific staining procedures
o G- banding (giemsa stain): most common
o Q-banding (quinacrine stain)
o R-banding (special treatment before staining)
26 Medical Genetics (2012-2013)
27. 27
o A uniform
system of
chromosome
classification is
internationally
accepted for
identification.
Resolution: ~ 400 bands per haploid karyotype
27 Medical Genetics (2012-2013)
28. 28
o The pattern of bands
on each chromosome is
numbered on each arm.
o For clarity only the G-
positive bands are
numbered
o Regions and
subregions are
numbered from the
centromere outward (1
is closest).550-band stage of condensation
28 Medical Genetics (2012-2013)
29. oAllow to precisely described:
oThe location of any band
oDNA sequences and genes within it
oits involvement in a chromosomal abnormality
oExample:
oBRCA1 (breast cancer susceptibility) gene
o17q21 long arm of chromosome 17 in region 21
ohuman cystic fibrosis gene
o7q31.2-q31.3 spanning both subregions 2 and 3
on the long arm of chromosome 7
29 Medical Genetics (2012-2013)
30. 30
o Metacentric
o Central centromere and equal arms length
o Submetacentric:
o Off-center centromeres and clearly
different arms length
o Acrocentric:
o Near the ends centromeres
o have small distinctive chromatin masses
(satellites) attached to short arms by
narrow stalks (secondary constrictions).
o Stalks contain hundreds of copies of genes
encoding rRNA as well as a variety of
repetitive sequences.
30 Medical Genetics (2012-2013)
31. 31
o C-banding:
o Staining the centromere and other regions containing
constitutive heterochromatin (sections of 1q, 9q and
16q adjacent to centromere and distal part of Yq)
o High resolution banding (prometaphase
banding):
o G- or R-banding of relatively uncondensed
chromosomes at early stage of mitosis (prophase or
prometaphase)
o Reveals 550 to 850 bands compared to 450 bands in
standard metaphase preparations
31 Medical Genetics (2012-2013)
33. 33
o DNA probes specific for individual chromosome,
chromosomal region, or genes are used to
o Identify particular chromosomal Rearrangements
o Rapidly diagnose the existence of an abnormal
chromosome number
33 Medical Genetics (2012-2013)
34. 34
Probe for factor VIII gene on the X
chromosome
A repetitive α-satellite DNA probe specific
for the centromere of chromosome 17
A whole-chromosome “paint” probe specific
for the X chromosome
34
FISH probes can be used with
both metaphase and interphase
Medical Genetics (2012-2013)
35. 35
o 2, 3 and even 4-color
applications are routinely
used to diagnose specific
deletions, duplications,
rearrangements in
metaphase and interphase
preperations.
35 Medical Genetics (2012-2013)
36. 36
o With highly specialized imaging procedure, 24 different
colors can be detected (SKY)
36 Medical Genetics (2012-2013)
37. 37
o Chromosome analysis at a genomic level by a
variety of array-based methods that use
comparative genomic hybridization (CGH).
o Assess the relative copy number of genomic DNA
sequences in a comprehensive genome wide
manner
o Complements and confirms conventional
karyotyping
o Can potentially provide very sensitive, high
resolution assessment of the genome
37 Medical Genetics (2012-2013)
39. o Germ cell (Constitutional) abnormality:
o present in all cells of the body
o must have been present very early in development,
o Somatic or acquired abnormality:
o present in only certain cells or tissues.
o mosaic with two different chromosome constitutions,
with both cell types deriving from the same zygote.
o Numerical or Structural
o May affect autosomes, sex chromosomes or both
Medical Genetics (2012-2013)39
40. oHeteroploid: A chromosome complement with any
chromosome number other than 46
1. Euploid: Exact multiple of haploid chromosome
number (n)
odiploid (2n) is normal for human somatic cells
ohaploid (n) is normal for germ cells
oTriploidy and Tetraploidy
oOccasionally observed in clinical material
oinfants can be liveborn
Medical Genetics (2012-2013)40
41. oHeteroploid: A chromosome complement with any
chromosome number other than 46
1. Euploid: Exact multiple of haploid chromosome
number (n)
odiploid (2n) is normal for human somatic cells
ohaploid (n) is normal for germ cells
oTriploidy and Tetraploidy
oOccasionally observed in clinical material
oinfants can be liveborn
Medical Genetics (2012-2013)41
42. oHeteroploid: A chromosome complement with any
chromosome number other than 46
2. Aneuploid: Any chromosome number other than
euploid
o Most common and clinically significant type of human
chromosome disorder
o Occures in at least 5% of all clinically recognized
pregnancies
o Trisomy three copies of a particular chromosome.
o Monosomy (less often) one representative of a
particular chromosome.
Medical Genetics (2012-2013)42
43. o Observed in 1% to 3% of recognized conceptions
o Most result from fertilization by two sperms
(dispermy).
o A proportion of the cases results from failure of
one of the two meiotic divisions (diploid egg or
sperm)
o Phenotype of triploid karyotype depends on
source of extra chromosome set:
o Extra-paternal set: abnormal placenta (partial
hydatidiform moles)
o Extra-maternal set: spontaneously aborted earlier in
pregnancy
Medical Genetics (2012-2013)43
44. o Much rarer than triploidy
o Absence of XXXY or XYYY suggests failure of
completion of an early cleavage division of
zygote
Medical Genetics (2012-2013)44
45. o Most common type
of trisomy in
liveborns is trisomy
21 (47,XX or XY,
+21)
o The chromosome
constitution seen in
95% of Down
syndrome.
Medical Genetics (2012-2013)45
46. o Other trisomies observed in liveborns include
trisomy18 and trisomy13
o It is notable that 13,18, and 21 are with lowest
number of genes located on them
o Trisomy for autosomes with greater number of genes is
lethal.
o Monosomy for entire chromosome is almost
always lethal.
o An important exception is monosomy for X chromosome
(Turner syndrome).
Medical Genetics (2012-2013)46
47. o Most commonly caused by meiotic nondisjunction
o Consequences of nondisjunction during meiosis I and II
are different.
Medical Genetics (2012-2013)47
48. o Nondisjunction has been associated with
aberrations in frequency or placement, or both, of
recombination events in meiosis-I.
o Too few (or even no) recombinations, or too close to
centromere or telomere favor non-disjunction.
o Another mechanism involves premature separation
of sister chromatids in meiosis I instead of II.
o The separated chromatids may by chance segregate to
oocyte or to polar body (unbalanced gamete)
Medical Genetics (2012-2013)48
49. o A gamete has an extra representative of more
than one chromosome
o Nondisjunction can take place at two successive meiotic
divisions
o Nondisjunction can by chance take place in both male
and female gametes simultaneously
o The resulting zygotes with unusual chromosome
numbers are extremely rare except for sex
chromosomes.
Medical Genetics (2012-2013)49
50. o Nondisjunction can occur in mitotic division after
zygote formation.
o at early cleavage clinically significant mosaicism
o In some malignant cell lines and some cell cultures
highly abnormal karyotypes
50 Medical Genetics (2012-2013)
51. o Three-color fluorescence in situ hybridization
analysis of human sperm
18:, X:, Y:
Medical Genetics (2012-2013)51
52. chr 18, aqua
chr X, green
chr Y, red
chr 18, aqua
chr X, green
chr 13, green
chr 21, red
o Prenatal evaluation of aneuploidy of chromosomes
13,18, 21, X and Y.
No need to
culture
cells
52 Medical Genetics (2012-2013)
53. o Structural rearrangements as a result of breakage
followed by reconstitution in an abnormal
combination
o Less common than aneuploidy
o Present in about 1 in 375 newborns.
o Chromosome rearrangements can occur
spontaneously at a low frequency and may be
induced by (clastogens)
o e.g., ionizing radiation, some viral infections, and many
chemicals.
o Like numerical abnormalities , structural
rearrangements may be present in all cells or in a
mosaic.
Medical Genetics (2012-2013)53
54. o May be defined as
o Balanced - no net gain or loss of chromosomal material
o Unbalanced – gain or loss of chromosomal material
o Stable: capable of passing through meiotic and mitotic
cell divisions unaltered
oTo be stable, a rearranged chromosome must have a
functional centromere and two telomeres
o Unstable
Medical Genetics (2012-2013)54
55. o The phenotype is likely abnormal.
o Any change that disturbs normal balance of
functional genes can result in abnormal
development.
o Deletions of part of chromosome partial monosomy
o Duplications of part of chromosome partial trisomy
o Detection:
o Karyotyping Large deletions or duplications (a few
million bp)
o FISH or microarray CGH Smaller deletions or
duplications
Medical Genetics (2012-2013)55
56. Two-color FISH of a case
with DiGeorge syndrome
(deletion of 22q11.2).
Medical Genetics (2012-2013)56
57. A. Duplication of chromosome
12p apparently normal
routine karyotype and
symptoms of Pallister-
Killian syndrome
B. Terminal deletion of chromosome
1p by array CGH in a patient with
mental retardation
C. 5 Mb de novo deletion of
chromosome 7q22 in a patient
with a complex abnormal
phenotype; originally undetected
by routine karyotyping.
Medical Genetics (2012-2013)57
58. o Small Submicroscopic
deletions, duplications
and translocations have
been detected
o changes of a telomere
region in patients with
idiopathic mental
retardation
o FISH array CGH of
telomeric and subtelomeric
regions may be indicated
in unexplained mental
retardation
chromosome 3p (red)
chromosome 11q (green).Medical Genetics (2012-2013)58
59. oLoss of a chromosome
segment resulting in
chromosome imbalance
oTerminal deletion: involves
loss of the chromosome tip
oInterstitial deletion: when
two breaks occur and the
material between them is lost
Medical Genetics (2012-2013)59
60. o Caused by:
o Chromosome break with a subsequent loss of acentric segment
o Unequal crossing over between misaligned homologous
chromosomes in some cases
o Abnormal segregation of a balanced translocation or inversion
Medical Genetics (2012-2013)60
61. o Clinical consequences depend upon:
o size of deleted segment
o number and function of lost genes
o Deletion one normal and one deleted
homologues
o monosomic for the lost genetic information
o Haploinsufficiency is a clinically reflected
consequence
o Inability of a single copy of the genetic material to
carry out functions normally carried out by two copies
Medical Genetics (2012-2013)61
62. o Can originate by
o Unequal crossing over
o abnormal segregation from meiosis in a carrier of a
translocation or inversion.
Medical Genetics (2012-2013)62
63. o Appears to be less harmful than deletion
o It may disrupt gene Often some phenotypic
abnormalities
o duplication of all or a portion of 12p Pallister-Killian
syndrome:
o characteristic craniofacial features, mental retardation, and
other birth defects
o likely related to trisomy or tetrasomy for specific genes in
duplicated region
Medical Genetics (2012-2013)63
64. o Very small, unidentified, frequently mosaic
o Usually called Supernumerary chromosomes or Extra
Structurally Abnormal Chromosomes
o Usually in addition to the normal chromosome complement
o Tiny marker chromosomes consist of little more than
centromeric heterochromatin
o Hard to specifically identify by banding
o Precise identification requires FISH with various paint probes
(SKY)
o Larger markers contain some material from one or both
arms
o The present genes are imbalanced
Medical Genetics (2012-2013)64
66. o Prenatal frequency of de novo supernumerary
chromosomes is estimated to be 1 in 2500
o Risk of fetal abnormality depends on marker
origin (from very low to 100%)
o Relatively high risk, Specific syndromes are associated
with bisatellited chromosome15 derived markers and
with centric portion of X.
o A subclass of marker chromosomes represents
small fragments of chromosome arms
o Somehow acquired centromere activity
Neocentromeres
Medical Genetics (2012-2013)66
67. o Marker chromosomes that
lack telomeric sequences
o Formed by breaks in the
two ends followed by
reuniting of the broken
ends
o Rare, but have been
detected for
every chromosome
Medical Genetics (2012-2013)67
68. o Mitotically stable if they contain a centromere
o Problems during disjunction at mitosis anaphase
oLarger and smaller rings may result due to breakage
followed by fusion at time of disjunction
Medical Genetics (2012-2013)68
69. o One arm is missing & the other is duplicated in a
mirror-image
o A person with 46 chromosomes carrying an
isochromosome
o Partial monosomy: single copy of one arm
o and partial trisomy: 3 copies of the second arm
o At least two mechanisms:
1. Misdivision through centromere in meiosis II
2. more commonly, exchange involving one arm of a
chromosome and its homolog (or sister chromatids)
isodicentric chromosomes
Medical Genetics (2012-2013)69
71. o The most common isochromosome is i(Xq) in some
individuals with Turner syndrome.
o i(18p) and i(12p) have also been seen
o Isochromosomes are frequently seen in karyotypes
of solid and hematological malignancies
Medical Genetics (2012-2013)71
72. o A rare type, in which two chromosome segments
each with a centromere, fuse end to end, with loss
of acentric fragments.
o from different chromosomes or from two chromatids of
a single chromosome
Medical Genetics (2012-2013)72
73. o May be mitotically stable, if
o one centromere is inactivated
o or the 2 centromeres coordinate their movement at
anaphase (formerly, pseudodicentric)
o Most commonly, involve
o the sex chromosome
o or the acrocentric chromosomes
Medical Genetics (2012-2013)73
74. o All chromosomal material is present but packaged
differently.
o Do not usually have a phenotypic effect.
o Carriers are likely to produce a high frequency of
unbalanced gametes.
o Increased risk of having abnormal offspring.
o Risk can range from 1 to 20% depending on
rearrangement.
o Chromosome breaks may possibly disrupt genes.
Medical Genetics (2012-2013)74
75. o 2 breaks on a single chromosome inversion
of the segment between the breaks
reconstitution at the original site
o Paracentric inversions do not involve the
centromere
o Don’t change the arms proportions identifiable
by FISH
o Pericentric inversions involve the centromere
o May change the proportions of the chromosome
arms and the banding pattern more easily
identifiable
Medical Genetics (2012-2013)75
76. • An inversion does not usually cause an abnormal
phenotype in carriers.
• A carrier is at risk to produce unbalanced
offspring.
• A loop is formed when the chromosomes pair at meiosis
• when recombination occurs, it can cause unbalanced
gametes.
Medical Genetics (2012-2013)76
77. o In paracentric: the risk that a carrier will have a
liveborn child with an abnormal karyotype is very
low
o The unbalanced recombinant chromosomes are
acentric or dicentric
o may not lead to viable offspring
Medical Genetics (2012-2013)77
78. o Pericentric: can lead to unbalanced gametes with
duplications and deficiencies.
o Each pericentric inversion is associated with a particular
risk of unbalanced karyotype (about 5% to 10%)
o Large pericentric inversions more likely to lead to viable
recombinant offspring
o because unbalanced segments in recombinants are smaller.
Medical Genetics (2012-2013)78
79. o Involve exchange of genetic material between two,
usually nonhomologous, chromosomes
o Two main types:
o Reciprocal
o Robertsonian.
Medical Genetics (2012-2013)79
80. o Exchange of broken-off fragments.
o Usually only 2 chromosomes involved
o Rare complex translocations involve 3
or more
o Relatively common
o found in about 1in 600 newborns.
o Commonly found in couples with 2 or
more spontaneous abortions and in
infertile males
o Usually harmless, although more
common in institutionalized
mentally retarded individuals.
o Associated with a high risk of
unbalanced gametes and
abnormal progeny.
Medical Genetics (2012-2013)80
81. o When chromosomes of a carrier of balanced
reciprocal translocation pair at meiosis
quadrivalent figure is formed (cross shaped)
Medical Genetics (2012-2013)81
82. o At anaphase, chromosomes segregate in one of
three ways:
o Alternate: the usual type of meiotic segregation
both types of gamete balanced.
o adjacent-1: homologous centromeres go to separate
daughter cells
o adjacent-2: homologous centromeres pass to same
daughter cell (rare)
Medical Genetics (2012-2013)82
84. o Additionally, balanced translocation chromosomes
can also segregate 3:1
o leading to gametes with 22 or 24 chromosomes
o Observed in 5-20% of sperm from balanced
translocation carrier, depending on specific
translocation
Medical Genetics (2012-2013)84
85. o Fusion of the long arms of 2 acrocentric
chromosomes at the centromeres with
loss of both short arms
o Results in 45 chromosomes only
o The loss of rRNA genes from the short arm
is not deleterious
o Can be monocentric or
pseudodicentric depending on
breakpoint location
Medical Genetics (2012-2013)85
86. o (13q14q) and (14q21q) are relatively common.
o 13q14q is found in about 1in1300
o Rare homozygotes for 13q14q exist
o Phenotypically normal with 44 chromosomes (no normal
13’s or 14’s).
o Phenotypically normal carriers have risk of
unbalanced gamete and thus offspring.
o Risk varies according to particular translocation and
sex of carrier
o carrier females have a higher risk of transmitting
translocation to an affected child
Medical Genetics (2012-2013)86
87. o A non-reciprocal type of translocation.
o A segment removed from one chromosome and inserted
into another in usual or inverted orientation.
o Rare, as they require 3 breaks
o Abnormal segregation in an insertion carrier can
produce offspring with deletion or duplication as
well as normal and balanced carriers.
o Average risk of producing an abnormal child is up
to 50%, and prenatal diagnosis is indicated
Medical Genetics (2012-2013)87
88. o Two or more different chromosome complements present
in an individual.
o May be either numerical or less commonly structural
o Typically detected by conventional karyotyping but can
be suspected in interphase FISH or array CGH.
o A common cause is nondisjunction in an early postzygotic
mitotic division.
o e.g., 47,+21 zygote loose the additional 21 and become
46/47,+21 mosaic.
o Effects on development vary with
o timing of nondisjunction event
o nature of chromosomal abnormality
o proportions of different chromosome complements present
o tissues affected.
Medical Genetics (2012-2013)88
89. Type
Approximate Proportion of
Abnormal Karyotypes
Aneuploidy
Autosomal trisomy 0.52
Autosomal monosomy <0.01
45,X 0.19
Triploidy 0.16
Tetraploidy 0.06
Other 0.07
Medical Genetics (2012-2013)89
91. o A standard set of abbreviations
o Indicates the nature of abnormality and the
technology used for analyses if performed
Medical Genetics (2012-2013)91
92. Abbrev. Meaning Example Condition
cen
del
der
dic
dup
fra
i
ins
inv
Centromere
Deletion
Derivative chr.
Dicentric chr.
Duplication
Fragile site
Isochromosome
Insertion
inversion
46,XX
46,XY
46,XX,del(5p)
der(1)
dic(X;Y)
46,Y,fra(X)(q27.3)
46,X,i(X)(q10)
inv(3)(p25q21)
Normal female karyotype
Normal male karyotype
Female with cri du chat s.
Translocation chr. Derived from
chr.1 with cen of chr.1
Translocation chr. with
centromeres of X and Y
Male with fragile X chr.
Female with isochr. Long arm X
Pericentric inv of chr.3
Medical Genetics (2012-2013)92
93. Abbrev. Meaning Example Condition
mar
mat
p
pat
q
r
rob
t
ter
Marker chr.
Maternal origin
Short arm
Paternal origin
Long arm
Ring
Robertsonian
translocation
Translocation
Terminal or
telomere
47,XX,+mar
47,XY,+der(1)mat
46,X,r(X)
Rob(13;21)(q10;q10)
46,XX,t(2;8)(q22;p21)
46,X,del(X)(pter
q21:)
Female with an extra
unidentified chr.
Male with an extra der(1) chr.
Inherited from mother
Female with ring X chr.
Reunion at centromeric region
of chr’s 13,21
Female with balanced
translocation, breaks in 2q22
and 8p21
Deletion distal to q21 (i.e.,
q21 is presentMedical Genetics (2012-2013)93
94. Abbrev. Meaning Example Condition
+
-
:
::
/
ish
arr
cgh
Gain of
Loss of
break
Break & join
mosaicism
In situ
hybridization
Array
Comparative
genomic hybrid.
47,XX,+21
45,XX,-22
5qter 5p15:
2pter2q22::8p218pter
46,XX/47,XX,+8
ish 22q11.2(D22S75 X2)
46,XX.ish
del(22)(q11.2)(D22S75-)
arr cgh 1-22(#BAC)x2,
X(#BAC)x2, Y(#BAC)x0
arr cgh 1-22(#BAC)x2,
X(#BAC)x1, Y(#BAC)x1
arr cgh 22q11.2(BAC name)x1
or
arr cgh 22q11.2(D22S75)x1
Female with trisomy 21
Female with monosomy 22
With deletion breakpoint in 5p15
Der(2) portion of t(2;8)
Probe for locus D22S75 in 22q11.2
(for DiGeorge S.). X2 = 2 signals
(normal)
Female normal G-banding, deletion
identified by FISH
Normal female array CGH pattern
Normal male array CGH
Loss of DiGeorge S. critical region
Medical Genetics (2012-2013)94
95. o Monosomies are more deleterious than trisomies
o Complete monosomies are generally not viable except for
monosomy X
o Complete trisomies are viable for chr. 13,18,21,X,Y.
o Phenotype in partial aneusomies depends on:
o Size of unbalanced segment
o Imbalance monosomic or trisomic
o Region of genome and genes involved
o In a mosaic karyotype, “all bets are off”
o Rings give a phenotype specific to genome region
involved, but are commonly mosaic.
o Inversions
o Pericentric: risk of birth defects in offspring increases with size
of inversion
o Paracentric: very low risk of abnormal phenotype
Medical Genetics (2012-2013)95
96. 96
o Most of the autosomal abnormalities can be diagnosed at
birth
o Most sex chromosome abnormalities, with the exception of
Turner syndrome, are not recognized clinically until
puberty
o Balanced rearrangements are rarely identified clinically
unless a carrier gives birth to a child with an unbalanced
chromosome complement
o unbalanced rearrangements are likely to come to clinical
attention because of abnormal appearance and delayed
physical and mental development
Medical Genetics (2012-2013)
97. o Expression of the disease phenotype of some
disorders, depends on parental origin of mutant
allele or abnormal chromosome
o Differences are the result of genomic imprinting.
o Imprinting is a normal process caused by
alterations in chromatin
o occur in the germline of one parent, but not the other
o occur at characteristic locations in the genome.
o includes the covalent modification of DNA, such as
omethylation of cytosine to form 5-methylcytosine
omodification or substitution in chromatin of specific histone
types
Medical Genetics (2012-2013)97
98. o Affects the expression of a gene but not its
primary DNA sequence
o It is a reversible form of gene inactivation but not a
mutation, (an epigenetic effect).
o Takes place during gametogenesis, before
fertilization
o After conception, the imprint controls gene
expression within the imprinted region in some or
all of the somatic tissues of the embryo.
o The imprinted state persists postnatally into
adulthood
Medical Genetics (2012-2013)98
100. 100
o Control over this conversion process appears to be
governed by DNA elements called imprinting
centers
o located within imprinted regions throughout the genome
o their precise mechanism of action is not known
o they initiate the epigenetic change in chromatin, which
then spreads outward along the chromosome over the
imprinted region.
Medical Genetics (2012-2013)
101. 101
o It is likely that as many as a hundred genes in the
human genome show imprinting effects
o Some regions contain a single imprinted gene;
others contain clusters, spanning in some cases well
over 1 Mb along a chromosome, of multiple
imprinted genes.
Medical Genetics (2012-2013)
103. 103
o Parental origin of genetic material (15q11-q13)
can have a profound effect on the clinical
expression of a defect.
Prader-Willi
Syndrome Angelman Syndrome
15q11-q13 deletion ~70% (paternal) ~70% (maternal)
Medical Genetics (2012-2013)
104. 104
o Prader-Willi is a relatively common dysmorphic syndrome:
o Obesity
o excessive and indiscriminate eating habits
o small hands short stature
o Hypogonadism
o mental retardation.
Medical Genetics (2012-2013)
106. 106
o Angelman syndrome is rare unusual:
o facial appearance
o short stature, severe mental retardation
o Spasticity
o Seizures
Medical Genetics (2012-2013)
107. 107
o The presence of two chromosomes, or portions
thereof, inherited from only one parent.
o Isodisomy: the identical chromosome is present in
duplicate
o Heterodisomy: if both homologues from one parent
are present
o About 30% of Prader-Willi syndrome
o do not have cytogenetically detectable deletions
o They have two normal chromosome 15's, both inherited
from the mother
o About 3%-5% of Angelman syndrome also have
uniparental disomy,
o Contain two intact chromosome 15's of paternal origin
Medical Genetics (2012-2013)
108. 108
o A few patients with Prader-Willi syndrome and
Angelman syndrome appear to have a defect in
the imprinting center itself
o the switch from female to male imprinting during
spermatogenesis or from male to female imprinting
during oogenesis fails to occur
o Fertilization by a sperm carrying an abnormally
persistent female imprint Prader-Willi syndrome
o fertilization of an egg that bears an inappropriately
persistent male imprint Angelman syndrome
Medical Genetics (2012-2013)
109. 109
o Mutations in the maternal copy of E6-AP
ubiquitin-protein ligase gene Angelman
syndrome
o The gene is located in 15q11-q13 and is maternally
expressed.
o It is likely that the large maternal 15q11-q13 deletions
and the uniparental disomy of paternal 15 seen in
Angelman syndrome cause the disorder
othey result in loss of the maternal copy of this critically
important, imprinted gene.
o Mutations in a single imprinted gene have not yet been
found in Prader-Willi syndrome.
Medical Genetics (2012-2013)
110. 110
Prader-Willi
Syndrome Angelman Syndrome
15q11-q13 deletion ~70% (paternal) ~70% (maternal)
Uniparental disomy ~30% (maternal) ~5% (paternal)
Single-gene mutation None detected E6-AP ubiquitin-protein
ligase (10% of total but
seen only in familial
cases)
Imprinting center
mutation
5% 5%
Unidentified <1% 10%-15%
Medical Genetics (2012-2013)
111. 111
o E.g. Beckwith-Wiedemann syndrome: Uniparental
disomy for a portion of chromosome 11 (11p15)
o an excess of paternal or a loss of maternal contribution
of genes, or both, including the insulin-like growth
factor 2 gene.
o Affected children are very large at birth
o have an enlarged tongue
o frequent protrusion of the umbilicus
o Life-threatening severe hypoglycemia and
development of malignant neoplasms of kidney,
adrenal, and liver.
Medical Genetics (2012-2013)
112. 11
o An abnormal pregnancy
o the placenta is converted into a mass
of tissue called a hydatid cyst.
o abnormal growth of the chorionic villi
(called a mole)
o the epithelium proliferates
o the stroma undergoes cystic cavitation
o A mole may be
o complete, with no fetus or normal
placenta present
o partial, with remnants of placenta and
perhaps a small atrophic fetus
Medical Genetics (2012-2013)
113. 113
o Most complete moles are diploid, 46,XX.
o The chromosomes are all paternal in origin,
o with rare exceptions, all genetic loci are homozygous.
o a single 23,X sperm fertilizes an ovum that lacks a
nucleus, and its chromosomes then double.
o Absence of any maternal contribution
o hyperplasia of the trophoblast
o grossly disorganized or absent fetal tissue
o About half of all cases of choriocarcinoma (a
malignant neoplasm of fetal, not maternal, tissue)
develop from hydatidiform moles.
Medical Genetics (2012-2013)
114. 114
oOvarian teratomas (benign tumors) arise
from 46,XX cells containing only maternal
chromosomes
oIn conclusion:
onormal fetal development requires both
maternal and paternal genetic contributions.
opaternal genome is especially important for
extraembryonic development,
omaternal genome is critical for fetal
development.
Medical Genetics (2012-2013)
115. 115
o Partial moles are triploid; in about two thirds of
cases
o the extra chromosome set is of paternal origin.
o Fetal development is severely abnormal in both
maternal or paternal origin, but the defects are
different.
o An extra paternal set results in abundant trophoblast
but poor embryonic development
o An extra maternal set results in severe retardation of
embryonic growth with a small, fibrotic placenta.
Medical Genetics (2012-2013)