This document summarizes the results of a study that identified 11 cases of amelogenin abnormalities in Belarusian males during forensic DNA analysis over a 15-year period. Nine cases showed absence of the AMELY marker, while two cases showed absence of the AMELX marker. In four AMELY-negative cases, deletion of both AMELY and the DYS458 marker was identified, suggesting an interstitial deletion on the Yp11.2 region. Three cases were identified as SRY-positive XX male syndrome based on amelogenin and Y-STR results. Genetic mechanisms like deletions, inversions, and mutations help explain the amelogenin abnormalities observed in these Belarusian
This document describes a study that developed a cost-effective screening test for detecting microdeletions on the Y chromosome associated with male infertility.
The researchers established a preliminary diagnostic screening test using a set of six primer pairs ("set-of-six") that could detect up to 95% of published Y microdeletion cases. They tested this set-of-six on 114 infertile men and found 10 microdeletions (8.8%), demonstrating the set-of-six could reliably identify microdeletions. Testing another 34 patients with just the set-of-six again found 3 microdeletions (8.8%). Their results were similar to literature frequencies, showing the set-of-six provides
This document discusses human genetics and genetic disorders. It covers inheritance and human variation, including dominant and recessive traits. Quantitative traits like skin and eye color are influenced by both genetic and environmental factors. The document also discusses diagnosing genetic diseases through amniocentesis and examines common genetic disorders such as autosomal dominant, autosomal recessive, and those linked to the X chromosome like color blindness and hemophilia. Pedigree charts are presented as a way to track the inheritance of these traits and disorders across generations.
Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of the enzyme alpha-galactosidase A, resulting in accumulation of globotriaosylceramide in tissues. It has a prevalence of 1 in 117,000 in Caucasians. Symptoms include neuropathic pain, angiokeratomas, renal failure, and cardiac and neurological problems. Diagnosis involves family history, symptoms, and enzyme/gene testing. Treatment is lifelong enzyme replacement therapy, though its effectiveness varies by organ involvement.
This document discusses human genetics and genetic disorders. It covers inheritance and human variation, including dominant and recessive traits. Quantitative traits like skin and eye color are influenced by both genetic and environmental factors. The document also discusses genetic diagnosis through amniocentesis and common genetic disorders such as autosomal dominant, autosomal recessive, and those linked to the X chromosome like color blindness and hemophilia. Pedigree charts are presented as a way to track inheritance of genetic traits across generations.
Concept of Sex chromosomes and autosomes,
Inheritance of X- linked genes – eye colour in Drosophila,
Inheritance of colour blindness in humans,
Inheritance of Y-linked Genes -Holandric genes in humans,
Sex influenced genes – baldness in humans
Sex-limited genes - feathering in domestic fowl
Types of blood groups and scope of geneticsRimsha Pahore
This document discusses blood group types and the scope of genetics. It describes the four main blood groups (A, B, AB, and O) which are determined by the presence or absence of antigens on red blood cells. The ABO blood group system and Rh blood group system are the two most important classification systems. Genetics has many important applications including understanding inheritance, disease risk, identity testing, treating diseases, understanding human origins, agriculture, ancient history, blood transfusions, prenatal testing, drug sensitivity, and pharmaceutical development.
This document discusses human genetics and genetic disorders. It covers inheritance and human variation, including dominant and recessive traits. Quantitative traits like skin and eye color are influenced by both genetic and environmental factors. The document also discusses diagnosing genetic diseases through amniocentesis and examines common genetic disorders like autosomal dominant and recessive traits as well as traits linked to the X chromosome. Pedigree charts are presented as a way to analyze inheritance patterns across generations.
This study analyzed mutations in the beta globin gene that cause beta-thalassemia in the Indian population. Genomic DNA was isolated from 118 beta-thalassemia major patient samples. A region of the HBB gene was amplified and sequenced in 19 samples. The most common mutation identified was IVS I-5 (G-C), which was found in homozygous form in 7 patients and heterozygous form in 8 patients. Other identified mutations include HBB:c. 47 G>A and HBB:c. 92 G>C. Identifying the prevalent mutations is important for prenatal diagnosis and genetic counseling to help control this common genetic disorder in India.
This document describes a study that developed a cost-effective screening test for detecting microdeletions on the Y chromosome associated with male infertility.
The researchers established a preliminary diagnostic screening test using a set of six primer pairs ("set-of-six") that could detect up to 95% of published Y microdeletion cases. They tested this set-of-six on 114 infertile men and found 10 microdeletions (8.8%), demonstrating the set-of-six could reliably identify microdeletions. Testing another 34 patients with just the set-of-six again found 3 microdeletions (8.8%). Their results were similar to literature frequencies, showing the set-of-six provides
This document discusses human genetics and genetic disorders. It covers inheritance and human variation, including dominant and recessive traits. Quantitative traits like skin and eye color are influenced by both genetic and environmental factors. The document also discusses diagnosing genetic diseases through amniocentesis and examines common genetic disorders such as autosomal dominant, autosomal recessive, and those linked to the X chromosome like color blindness and hemophilia. Pedigree charts are presented as a way to track the inheritance of these traits and disorders across generations.
Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of the enzyme alpha-galactosidase A, resulting in accumulation of globotriaosylceramide in tissues. It has a prevalence of 1 in 117,000 in Caucasians. Symptoms include neuropathic pain, angiokeratomas, renal failure, and cardiac and neurological problems. Diagnosis involves family history, symptoms, and enzyme/gene testing. Treatment is lifelong enzyme replacement therapy, though its effectiveness varies by organ involvement.
This document discusses human genetics and genetic disorders. It covers inheritance and human variation, including dominant and recessive traits. Quantitative traits like skin and eye color are influenced by both genetic and environmental factors. The document also discusses genetic diagnosis through amniocentesis and common genetic disorders such as autosomal dominant, autosomal recessive, and those linked to the X chromosome like color blindness and hemophilia. Pedigree charts are presented as a way to track inheritance of genetic traits across generations.
Concept of Sex chromosomes and autosomes,
Inheritance of X- linked genes – eye colour in Drosophila,
Inheritance of colour blindness in humans,
Inheritance of Y-linked Genes -Holandric genes in humans,
Sex influenced genes – baldness in humans
Sex-limited genes - feathering in domestic fowl
Types of blood groups and scope of geneticsRimsha Pahore
This document discusses blood group types and the scope of genetics. It describes the four main blood groups (A, B, AB, and O) which are determined by the presence or absence of antigens on red blood cells. The ABO blood group system and Rh blood group system are the two most important classification systems. Genetics has many important applications including understanding inheritance, disease risk, identity testing, treating diseases, understanding human origins, agriculture, ancient history, blood transfusions, prenatal testing, drug sensitivity, and pharmaceutical development.
This document discusses human genetics and genetic disorders. It covers inheritance and human variation, including dominant and recessive traits. Quantitative traits like skin and eye color are influenced by both genetic and environmental factors. The document also discusses diagnosing genetic diseases through amniocentesis and examines common genetic disorders like autosomal dominant and recessive traits as well as traits linked to the X chromosome. Pedigree charts are presented as a way to analyze inheritance patterns across generations.
This study analyzed mutations in the beta globin gene that cause beta-thalassemia in the Indian population. Genomic DNA was isolated from 118 beta-thalassemia major patient samples. A region of the HBB gene was amplified and sequenced in 19 samples. The most common mutation identified was IVS I-5 (G-C), which was found in homozygous form in 7 patients and heterozygous form in 8 patients. Other identified mutations include HBB:c. 47 G>A and HBB:c. 92 G>C. Identifying the prevalent mutations is important for prenatal diagnosis and genetic counseling to help control this common genetic disorder in India.
Fragile X Syndrome Mutation by Methylation Sensitive PCRrosstroop
This document discusses the diagnosis of Fragile X syndrome through methylation-sensitive PCR (MS-PCR) testing. It provides background information on the characteristics, inheritance, and FMR1 gene mutation associated with Fragile X syndrome. It then describes the MS-PCR diagnostic method, which analyzes both the methylation status of the FMR1 promoter region and the number of CGG repeats to determine if a sample is normal, a premutation, or has a full mutation associated with Fragile X syndrome. The document concludes by validating the MS-PCR method against the gold standard Southern blot technique.
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 document discusses human genetics and inheritance. It begins by describing human chromosomes, including that humans have 46 total chromosomes, with two sex chromosomes (XX for females and XY for males) that determine sex. The rest are autosomal chromosomes. It then discusses several examples of human genetic traits, including blood type, which is determined by genes on certain chromosomes. Specific genetic disorders like sickle cell anemia and cystic fibrosis are caused by mutations in single genes. The document also covers sex-linked traits, which are inherited differently since they are located on the X or Y chromosome.
This document discusses human genetics, including genetic and environmental factors that contribute to variation between individuals. It describes quantitative traits like height and hair color that are influenced by multiple genes as well as qualitative traits like handedness that are determined by a single gene. The document also covers blood typing, karyotyping, genetic disorders, sex-linked inheritance, autosomal disorders, and sex chromosome disorders.
The document discusses various genetics topics including mitosis, meiosis, chromosomes, genes, alleles, genotypes, phenotypes, dominant and recessive traits, sex-linked traits, common genetic disorders like Down syndrome, and monogenic inheritance patterns. It provides examples of inheritance calculations for traits like albinism, PKU, sickle cell anemia, dwarfism, and hemophilia.
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 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
This document provides an overview of fundamentals of genetics. It discusses that humans have 23 chromosome pairs, 30,000-40,000 genes, and over 3 billion base pairs. The human genome project was completed in 2000. Genetics is studied to understand chromosomal abnormalities in pregnancies that can cause fetal loss, birth defects, or genetic diseases. Inheritance patterns can be monogenic/Mendelian including autosomal dominant, autosomal recessive, and X-linked, or polygenic/multifactorial. Genetic testing is used for diagnosis, carrier detection, early intervention and prevention of disease.
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.
Identification of a Novel Mutation (p.G328W) in the NR5A1 Gene in a Boy with ...CrimsonPublishersGJEM
This document summarizes a case report of a 46,XY newborn with ambiguous genitalia presenting with a novel mutation in the NR5A1 gene. The key points are:
- The newborn presented with micropenis, hypospadias, and bilateral inguinal gonads. Hormone testing showed a normal testosterone response to hCG.
- Genetic testing identified a novel heterozygous p.G328W mutation in the NR5A1 gene, which had not been previously reported. This mutation occurred de novo.
- The mutation affects a highly conserved residue in the ligand binding domain of SF1. While adrenal function was normal, the mutation is believed
Dr. Wiskott noted an inherited condition in a German family that affected three boys who died of the same illness involving bruising, eczema, bloody diarrhea, and infections. The boys died from bleeding in their digestive tracts and blood infections. Dr. Wiskott observed that the condition seemed to only affect boys in the family and was inherited in nature.
The document discusses key concepts in human genetics. It defines several genetic terms like heredity, allele frequency, mutation, gene pool, and genetic drift. It also outlines common patterns of inheritance including autosomal dominant, autosomal recessive, sex-linked dominant, sex-linked recessive, and sex-influenced traits. Examples are given for each pattern. The document also describes common chromosome anomalies like polyploidy, aneuploidy, and structural abnormalities. Specific conditions resulting from genetic disorders are discussed like cystic fibrosis, sickle cell anemia, and phenylketonuria. Behavioral disorders with a genetic basis like schizophrenia and drug addiction are also summarized.
This document discusses genes that have more than two alleles (poly-allelic genes). It provides examples of poly-allelic genes, including the ABO blood type gene, which has three alleles that produce the A, B, and O antigens. The document explains that poly-allelic genes can generate more genotypes than di-allelic genes. It also discusses X-linked inheritance and provides Drosophila eye color as an example, noting that X-linked traits are observed disproportionately in males.
Human body cells contain 23 pairs of chromosomes, with one chromosome of each pair inherited from each parent. Chromosomes are made of DNA and contain genes arranged in linear order that encode for proteins. Alterations in genes or chromosomes, such as changes in chromosome number like trisomies, or structural changes like deletions, can alter the amount or sequence of proteins produced and cause diseases.
This document provides information on genetic concepts including genes, DNA, chromosomes, genotypes and phenotypes. It defines key terms and describes patterns of inheritance such as dominant, recessive, X-linked, autosomal and codominant traits. Examples are given of human genetic disorders and their inheritance patterns. Questions at the end test understanding of calculating inheritance probabilities and determining modes of inheritance from pedigree charts.
Genetic syndromes can be caused by chromosomal abnormalities such as aneuploidy, where there is an extra or missing chromosome, or structural abnormalities like deletions, duplications, inversions, or translocations of chromosomal segments. Detection of chromosomal abnormalities is important in animal breeding since it can impact reproduction and production. Genetic testing helps reduce the incidence of genetically abnormal offspring by identifying carrier animals. Untested breeding can spread genetic disorders and cause huge economic losses for farmers.
The document provides an overview of basic genetics concepts including genes, chromosomes, DNA, genotypes, phenotypes, dominant and recessive traits, and patterns of inheritance. It discusses Mendel's laws of inheritance and how they can be used to calculate inheritance probabilities. It also summarizes different modes of inheritance including autosomal recessive, autosomal dominant, X-linked, codominant, and mitochondrial inheritance and provides examples for each.
Biology - Chp14 - Human Heredity - NotesMr. Walajtys
This document summarizes information about human heredity and genetics. It discusses that human genetics is now better understood due to projects like the Human Genome Project. It describes that humans have 23 pairs of chromosomes, including sex chromosomes that determine gender. Most traits are influenced by multiple genes and the environment. Examples of genetic disorders like cystic fibrosis, sickle cell disease, and PKU are provided to explain recessive and dominant alleles. The role of pedigrees and karyotypes in studying human genetics is also mentioned.
The document discusses human genetics and inheritance patterns. It covers topics like human chromosomes, genetic disorders, studying the human genome, and inheritance of traits. Key points include that humans have 23 pairs of chromosomes, including one pair of sex chromosomes (X and Y); genetic disorders can be caused by changes in chromosomes or DNA; and traits can be inherited in sex-linked patterns when located on the X or Y chromosome.
The role of Y chromosome and mitochondrial DNA in forensic scienceALEMU TEBEJE
Basic Characteristic of SNPs
Forensic Applications of SNP Profiling
HLA-DQA1 LOCUS
Existing and Potential Applications
Application of SNPs for Forensic Identification
Potential Application of SNP for Phenotyping
Techniques
Inheritance of some genetic diseases is linked to a sex chromosome. These disorders are also called sex-linked diseases. Approximately 800 various genes were identified on the X chromosome. The Y chromosome contains only 45 genes, which are predominantly connected with the determination of male sex and with spermatogenesis. For this reason, sex-linked diseases are primarily determined by the presence of abnormal variations of genes located on the X chromosome. Tt has become customary to refer to sex-linked diseases as X-linked diseases.
Fragile X Syndrome Mutation by Methylation Sensitive PCRrosstroop
This document discusses the diagnosis of Fragile X syndrome through methylation-sensitive PCR (MS-PCR) testing. It provides background information on the characteristics, inheritance, and FMR1 gene mutation associated with Fragile X syndrome. It then describes the MS-PCR diagnostic method, which analyzes both the methylation status of the FMR1 promoter region and the number of CGG repeats to determine if a sample is normal, a premutation, or has a full mutation associated with Fragile X syndrome. The document concludes by validating the MS-PCR method against the gold standard Southern blot technique.
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 document discusses human genetics and inheritance. It begins by describing human chromosomes, including that humans have 46 total chromosomes, with two sex chromosomes (XX for females and XY for males) that determine sex. The rest are autosomal chromosomes. It then discusses several examples of human genetic traits, including blood type, which is determined by genes on certain chromosomes. Specific genetic disorders like sickle cell anemia and cystic fibrosis are caused by mutations in single genes. The document also covers sex-linked traits, which are inherited differently since they are located on the X or Y chromosome.
This document discusses human genetics, including genetic and environmental factors that contribute to variation between individuals. It describes quantitative traits like height and hair color that are influenced by multiple genes as well as qualitative traits like handedness that are determined by a single gene. The document also covers blood typing, karyotyping, genetic disorders, sex-linked inheritance, autosomal disorders, and sex chromosome disorders.
The document discusses various genetics topics including mitosis, meiosis, chromosomes, genes, alleles, genotypes, phenotypes, dominant and recessive traits, sex-linked traits, common genetic disorders like Down syndrome, and monogenic inheritance patterns. It provides examples of inheritance calculations for traits like albinism, PKU, sickle cell anemia, dwarfism, and hemophilia.
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 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
This document provides an overview of fundamentals of genetics. It discusses that humans have 23 chromosome pairs, 30,000-40,000 genes, and over 3 billion base pairs. The human genome project was completed in 2000. Genetics is studied to understand chromosomal abnormalities in pregnancies that can cause fetal loss, birth defects, or genetic diseases. Inheritance patterns can be monogenic/Mendelian including autosomal dominant, autosomal recessive, and X-linked, or polygenic/multifactorial. Genetic testing is used for diagnosis, carrier detection, early intervention and prevention of disease.
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.
Identification of a Novel Mutation (p.G328W) in the NR5A1 Gene in a Boy with ...CrimsonPublishersGJEM
This document summarizes a case report of a 46,XY newborn with ambiguous genitalia presenting with a novel mutation in the NR5A1 gene. The key points are:
- The newborn presented with micropenis, hypospadias, and bilateral inguinal gonads. Hormone testing showed a normal testosterone response to hCG.
- Genetic testing identified a novel heterozygous p.G328W mutation in the NR5A1 gene, which had not been previously reported. This mutation occurred de novo.
- The mutation affects a highly conserved residue in the ligand binding domain of SF1. While adrenal function was normal, the mutation is believed
Dr. Wiskott noted an inherited condition in a German family that affected three boys who died of the same illness involving bruising, eczema, bloody diarrhea, and infections. The boys died from bleeding in their digestive tracts and blood infections. Dr. Wiskott observed that the condition seemed to only affect boys in the family and was inherited in nature.
The document discusses key concepts in human genetics. It defines several genetic terms like heredity, allele frequency, mutation, gene pool, and genetic drift. It also outlines common patterns of inheritance including autosomal dominant, autosomal recessive, sex-linked dominant, sex-linked recessive, and sex-influenced traits. Examples are given for each pattern. The document also describes common chromosome anomalies like polyploidy, aneuploidy, and structural abnormalities. Specific conditions resulting from genetic disorders are discussed like cystic fibrosis, sickle cell anemia, and phenylketonuria. Behavioral disorders with a genetic basis like schizophrenia and drug addiction are also summarized.
This document discusses genes that have more than two alleles (poly-allelic genes). It provides examples of poly-allelic genes, including the ABO blood type gene, which has three alleles that produce the A, B, and O antigens. The document explains that poly-allelic genes can generate more genotypes than di-allelic genes. It also discusses X-linked inheritance and provides Drosophila eye color as an example, noting that X-linked traits are observed disproportionately in males.
Human body cells contain 23 pairs of chromosomes, with one chromosome of each pair inherited from each parent. Chromosomes are made of DNA and contain genes arranged in linear order that encode for proteins. Alterations in genes or chromosomes, such as changes in chromosome number like trisomies, or structural changes like deletions, can alter the amount or sequence of proteins produced and cause diseases.
This document provides information on genetic concepts including genes, DNA, chromosomes, genotypes and phenotypes. It defines key terms and describes patterns of inheritance such as dominant, recessive, X-linked, autosomal and codominant traits. Examples are given of human genetic disorders and their inheritance patterns. Questions at the end test understanding of calculating inheritance probabilities and determining modes of inheritance from pedigree charts.
Genetic syndromes can be caused by chromosomal abnormalities such as aneuploidy, where there is an extra or missing chromosome, or structural abnormalities like deletions, duplications, inversions, or translocations of chromosomal segments. Detection of chromosomal abnormalities is important in animal breeding since it can impact reproduction and production. Genetic testing helps reduce the incidence of genetically abnormal offspring by identifying carrier animals. Untested breeding can spread genetic disorders and cause huge economic losses for farmers.
The document provides an overview of basic genetics concepts including genes, chromosomes, DNA, genotypes, phenotypes, dominant and recessive traits, and patterns of inheritance. It discusses Mendel's laws of inheritance and how they can be used to calculate inheritance probabilities. It also summarizes different modes of inheritance including autosomal recessive, autosomal dominant, X-linked, codominant, and mitochondrial inheritance and provides examples for each.
Biology - Chp14 - Human Heredity - NotesMr. Walajtys
This document summarizes information about human heredity and genetics. It discusses that human genetics is now better understood due to projects like the Human Genome Project. It describes that humans have 23 pairs of chromosomes, including sex chromosomes that determine gender. Most traits are influenced by multiple genes and the environment. Examples of genetic disorders like cystic fibrosis, sickle cell disease, and PKU are provided to explain recessive and dominant alleles. The role of pedigrees and karyotypes in studying human genetics is also mentioned.
The document discusses human genetics and inheritance patterns. It covers topics like human chromosomes, genetic disorders, studying the human genome, and inheritance of traits. Key points include that humans have 23 pairs of chromosomes, including one pair of sex chromosomes (X and Y); genetic disorders can be caused by changes in chromosomes or DNA; and traits can be inherited in sex-linked patterns when located on the X or Y chromosome.
The role of Y chromosome and mitochondrial DNA in forensic scienceALEMU TEBEJE
Basic Characteristic of SNPs
Forensic Applications of SNP Profiling
HLA-DQA1 LOCUS
Existing and Potential Applications
Application of SNPs for Forensic Identification
Potential Application of SNP for Phenotyping
Techniques
Inheritance of some genetic diseases is linked to a sex chromosome. These disorders are also called sex-linked diseases. Approximately 800 various genes were identified on the X chromosome. The Y chromosome contains only 45 genes, which are predominantly connected with the determination of male sex and with spermatogenesis. For this reason, sex-linked diseases are primarily determined by the presence of abnormal variations of genes located on the X chromosome. Tt has become customary to refer to sex-linked diseases as X-linked diseases.
Whole-exome sequencing of three affected family members identified a frameshift mutation in LAMB3 as the cause of dominant hypoplastic amelogenesis imperfecta in the family. The mutation was a single base pair insertion that caused a premature stop codon and co-segregated with the disease phenotype in the family. This is the first report of dominant AI caused by a heterozygous LAMB3 mutation, as LAMB3 mutations typically cause the skin blistering disorder junctional epidermolysis bullosa in a recessive manner. Identification of the pathogenic variant was achieved without prior linkage analysis through filtering of variants shared between the affected individuals sequenced.
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is an open access international journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
This document summarizes key concepts about the chromosomal basis of inheritance from genetics. It discusses how genes are located on chromosomes and segregate during meiosis according to Mendel's laws. It describes classic experiments by Morgan using fruit flies that provided evidence linking genes to chromosomes. The document explains genetic linkage, recombination, and how crossover during meiosis generates genetic variation. It also discusses different types of chromosomal abnormalities and how they can cause genetic disorders.
This document summarizes key concepts about the chromosomal basis of inheritance from genetics research in the early 20th century. It discusses how Mendel's laws of inheritance can be explained by the behavior of chromosomes and genes during meiosis and fertilization. The work of Thomas Hunt Morgan with fruit flies provided evidence that genes are located on chromosomes. His experiments showed that linked genes tend to be inherited together but can assort independently at low frequencies, due to chromosome crossover during meiosis. This led to the theory that genes reside at specific loci on chromosomes and explained how genetic variation arises.
Thomas Hunt Morgan was awarded the 1933 Nobel Prize in Physiology or Medicine for his discoveries concerning the role of chromosomes in heredity. Through experiments with fruit flies, Morgan demonstrated that genes are located on chromosomes and are passed from parents to offspring. His work established genetics as an experimental science and provided evidence that chromosomes behave in predictable ways during the inheritance of traits.
Prenatal Diagnosis of Denys-Drash Syndromenavasreni
Denys-Drash syndrome consists of the triad of progressive nephropathy characterised by diffuse
mesangial sclerosis (DMS), genital abnormalities, and Wilms tumour. Nephropathy may range
from early onset proteinuria to nephrotic syndrome to end stage renal failure. Genital malformations affects both external and internal genitalia. It may range from penoscrotal hypospadias,
bilateral cryptorchidism to an enlarged clitoris with fused labia and a urogenital sinus to atrophic
uterus to streak ovaries or dysgenetic testes. The risk of developing Wilms’ tumor may be as high
as 50%.
Denys-Drash syndrome consists of the triad of progressive nephropathy characterised by diffuse mesangial sclerosis (DMS), genital abnormalities, and Wilms tumour. Nephropathy may range from early onset proteinuria to nephrotic syndrome to end stage renal failure. Genital malformations affects both external and internal genitalia...
Prenatal Diagnosis of Denys-Drash Syndromepateldrona
This document presents a case study of prenatal diagnosis of Denys-Drash Syndrome. Antenatal ultrasound found oligohydramnios, failure of fetal growth, and suspected ambiguous genitalia. Chromosomal microarray analysis identified a 20 kilobase pair microdeletion in the WT1 gene on chromosome 11p13, which is associated with Denys-Drash Syndrome. This syndrome consists of nephropathy, genital abnormalities, and risk of Wilms' tumor. The deletion affected exonic and intronic regions of the WT1 gene. Postnatal outcomes of Denys-Drash Syndrome can include genital malformations and early-onset nephropathy evolving into end-stage renal failure.
Prenatal Diagnosis of Denys-Drash Syndromeeshaasini
Denys-Drash syndrome consists of the triad of progressive nephropathy characterised by diffuse
mesangial sclerosis (DMS), genital abnormalities, and Wilms tumour. Nephropathy may range
from early onset proteinuria to nephrotic syndrome to end stage renal failure. Genital malformations affects both external and internal genitalia. It may range from penoscrotal hypospadias,
bilateral cryptorchidism to an enlarged clitoris with fused labia and a urogenital sinus to atrophic
uterus to streak ovaries or dysgenetic testes. The risk of developing Wilms’ tumor may be as high
as 50%.
Prenatal Diagnosis of Denys-Drash Syndromegeorgemarini
Denys-Drash syndrome consists of the triad of progressive nephropathy characterised by diffuse mesangial sclerosis (DMS), genital abnormalities, and Wilms tumour. Nephropathy may range from early onset proteinuria to nephrotic syndrome to end stage renal failure. Genital malformations affects both external and internal genitalia...
Prenatal Diagnosis of Denys-Drash Syndromekomalicarol
Denys-Drash syndrome consists of the triad of progressive nephropathy characterised by diffuse
mesangial sclerosis (DMS), genital abnormalities, and Wilms tumour. Nephropathy may range
from early onset proteinuria to nephrotic syndrome to end stage renal failure. Genital malformations affects both external and internal genitalia. It may range from penoscrotal hypospadias,
bilateral cryptorchidism to an enlarged clitoris with fused labia and a urogenital sinus to atrophic
uterus to streak ovaries or dysgenetic testes. The risk of developing Wilms’ tumor may be as high
as 50%.
Prenatal Diagnosis of Denys-Drash SyndromeSarkarRenon
Denys-Drash syndrome consists of the triad of progressive nephropathy characterised by diffuse mesangial sclerosis (DMS), genital abnormalities, and Wilms tumour. Nephropathy may range from early onset proteinuria to nephrotic syndrome to end stage renal failure.
Prenatal Diagnosis of Denys-Drash SyndromeAnonIshanvi
Denys-Drash syndrome consists of the triad of progressive nephropathy characterised by diffuse mesangial sclerosis (DMS), genital abnormalities, and Wilms tumour. Nephropathy may range from early onset proteinuria to nephrotic syndrome to end stage renal failure. Genital malformations affects both external and internal genitalia...
20150918 E. Pompilii - Microarray in diagnosi prenatale: la complessità della...Roberto Scarafia
Eva Pompilii, MD
Genetic Counselor , TOMA Advanced Biomedical Assays, S.p.A.,
Gynepro Medical Bologna, Policlinico S.Orsola Malpighi Bologna
• OBJECTIVES:
At present, a precise guideline establishing chromosome microarray analysis (CMA) applications and platforms in the prenatal setting does not exist. The actual controversial
question is whether CMA technologies can or should shortly replace the standard karyotype in prenatal diagnosis practice
• CONCLUSIONS:
Presently CMA analysis can be considered a second-tier diagnostic test to be used after a standard karyotype in selected group of pregnancies, such as those with single
(apparently isolated) or multiple US fetal abnormalities, with de novo chromosomal rearrangements, even if apparently balanced, and those with supernumerary markers chromosomes
This document provides an overview of cytogenetics and chromosomal abnormalities. It begins with the history of cytogenetics, including the discovery of human chromosomes in 1882 and establishing the normal human karyotype of 46 chromosomes in 1956. It describes laboratory techniques for culturing and staining chromosomes, including various banding techniques. It discusses clinical cytogenetics and genetic counseling. It provides detailed explanations and examples of different types of numerical and structural chromosomal abnormalities, including aneuploidies, polyploidies, translocations, inversions, deletions and more. It explains the associated phenotypes and inheritance patterns of many common chromosomal syndromes.
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
This document provides an overview of biological inheritance. It discusses genes and alleles, Mendel's laws of inheritance from his early genetic studies with pea plants, the location of genes on chromosomes, determining sex based on sex chromosomes, inheritance linked to sex chromosomes, and mutations. The key topics covered are Mendel's principles of uniformity, segregation, and independent assortment which established the foundations of modern genetics. It also examines gene location and linkage, sex determination, sex-linked inheritance patterns, and the types and causes of genetic mutations.
Similar to Amelogenin test abnormalities revealed in Belaruisan population during forensic DNA analysis (20)
Amelogenin test abnormalities revealed in Belaruisan population during forensic DNA analysis
1. Amelogenin test abnormalities revealed in Belarusian population
during forensic DNA analysis
Sergey Borovko *, Alena Shyla, Victorya Korban, Alexandra Borovko
State Committee of Forensic Examinations of the Republic of Belarus, Volodarskiy str. 2a, 220030 Minsk, Belarus
1. Introduction
Human gender determination based on the amelogenin gene is
widely used in many fields: prenatal diagnosis of X-linked
diseases (e.g. Duchenne muscular dystrophy and haemophilia),
diagnosis of sex chromosome aneuploidies, preimplantation
diagnosis and monitoring patients after sexmismatched bone
marrow transplant, archaeological analysis, DNA databasing,
blood sample storage. The accurate gender determination of
biological samples is essential in forensic casework, paternity
testing and person identification [1,2].
The amelogenin gene is a single copy gene, homologues of
which amelogenin X (AMELX) and amelogenin Y (AMELY) are
located on Xp22.1–Xp22.3 and Yp11.2, respectively. Homologues
AMELX and AMELY differ in both size and sequence. The
amelogenin locus has been incorporated in various commercial
short tandem repeat (STR) multiplex kits for human gender
identification. The most commonly used amelogenin primer set
flanks a 6 bp deletion within intron 1 of AMELX and produces
fragments of 106 bp and 112 bp for the X and Y-chromosomes,
respectively [3–6].
Amplification failure of the AMELY in the male samples can
cause misidentification of the biological sample as a female if the
other information of the sample is not considered or not available.
Similarly, mutations of AMELX in males can be responsible for
AMELX dropout although the genotype of the biological sample
would still be identified as a male due to amplification of AMELY.
Cases of amelogenin-negative males have been detected
worldwide. Genetic mechanisms underlying AMELY dropout
involve deletions of different size encompassing AMELY locus,
mutations in the primer-binding region of AMELY allele in the
lesser extent [1,5]. Deletions on Yp11.2 region as a major cause of
AMELY null allele are often combined with the absence of adjacent
Y-STR loci DYS456 and/or DYS458 [1,2,6–12].
Translocations between distal Xp and Yp result in the
generation of 46,XX males, the majority of whom display a male
phenotype due to transfer of the sex-determining region Y (SRY)
gene onto the short arm of the X-chromosome (SRY-positive XX
male syndrome) [13,14]. The XX male syndrome or 46,XX
testicular disorder of sex development (OMIM ID #400045) occurs
very rare with a frequency of 1:20,000–1:30,000 male newborns
and was first described by de la Chapelle et al. in 1964
Forensic Science International: Genetics 15 (2015) 98–104
A R T I C L E I N F O
Keywords:
Amelogenin X (AMELX)
Amelogenin Y (AMELY)
Null allele
Deletion
Short tandem repeat (STR)
XX male syndrome
A B S T R A C T
Study of gender markers is a part of routine forensic genetic examination of crime scene and reference
samples, paternity testing and personal identification. Amelogenin locus as a gender marker is included
in majority of forensic STR kits of different manufacturers. In current study we report 11 cases of
amelogenin abnormalities identified in males of Belarusian origin: 9 cases of AMELY dropout and 2 cases
of AMELX dropout. Cases were obtained from forensic casework (n = 9) and paternity testing (n = 2)
groups. In 4 out of 9 AMELY-negative cases deletion of AMELY was associated with the loss of DYS458
marker. In addition, we identified 3 males with SRY-positive XX male syndrome. Deletion of the long arm
of the Y-chromosome was detected in two XX males. Loss of the major part of the Y-chromosome was
identified in the third XX male. The presence of two X-chromosomes in XX males was confirmed with the
use of Mentype1
Argus X-8 PCR Amplification Kit. AMELY null allele observed in 2 out of 9 cases with
AMELY dropout can be caused by mutation in the primer-binding site of AMELY allele. Primer-binding
site mutations of AMELX can result in AMELX dropout identified in 2 cases with amplification failure of
AMELX. Our study represents the first report and molecular genetic investigation of amelogenin
abnormalities in the Belarusian population.
ß 2014 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author. Tel.: +375 29 629 74 91; fax: +375 17 218 74 03.
E-mail address: s_borovko@mail.ru (S. Borovko).
Contents lists available at ScienceDirect
Forensic Science International: Genetics
journal homepage: www.elsevier.com/locate/fsig
http://dx.doi.org/10.1016/j.fsigen.2014.10.014
1872-4973/ß 2014 Elsevier Ireland Ltd. All rights reserved.
2. [13–16]. Since then up to 2006 approximately 250 cases with
46,XX male syndrome were published in the world literature,
mostly as individual cases. On the basis of the SRY gene analysis
46,XX males can be divided into SRY-positive (90%) and SRY-
negative (10%) groups [16].
Cases of AMELX dropout in males have been reported in several
papers [5,14,17–19]. A primer-binding site point mutations in
AMELX allele have been detected in all males displayed only the Y
allele from amelogenin amplification in these studies.
During 15-year expert practice in forensic DNA analysis we
analyzed more than 30,000 forensic cases and more than 4000
paternity testing cases. Of this amount of cases we collected 11
cases with amelogenin abnormalities (AMELY or AMELX drop-
outs) identified in Belarusian population. AMELX and AMELY null
alleles were revealed with either AmpF‘STR1
Identifiler1
Plus
PCR Amplification Kit (Identifiler1
Plus Kit) or GlobalFiler1
PCR
Amplification Kit (GlobalFiler1
Kit). To elucidate genetic mecha-
nisms underlying anomalous amplification of the amelogenin
locus in Belarusian males we used AmpF‘STR1
Yfiler1
PCR
Amplification Kit (Yfiler1
Kit) for Y-STRs profiling, Mentype1
Argus X-8 PCR Amplification Kit (Mentype1
Argus X-8 Kit) for
X-STRs and amelogenin analysis, Quantifiler1
Y Human Male
DNA Quantification Kit (Quantifiler1
Y Kit) for the detection of
the SRY gene.
2. Materials and methods
All 11 amelogenin-negative cases we describe here were
analyzed in different periods of time during our 15-year expert
practice in forensic DNA analysis. 9 cases were obtained from
crime casework groups and 2 cases (father–son sample pairs) were
discovered during routine paternity testing. The choice of the kits
used for the genetic analysis of these samples was dependent on
the above-mentioned factors (e.g., availability of various kits) and
also on the genetic nature of the revealed amelogenin abnormali-
ties in the samples.
Depending on the source of a biological sample (blood stain
samples, buccal swabs, etc.) and its quality genomic DNA was
extracted using one of the following methods: Chelex-100 method
(Bio-Rad, USA), phenol–chloroform extraction [20], and such kits
as PrepFiler1
Forensic DNA Extraction Kit (Applied Biosystems),
NucleoSpin1
Tissue (Macherey-Nagel, Germany).
Autosomal STRs and amelogenin were amplified using either
AmpF‘STR1
Identifiler1
Plus PCR Amplification Kit (Applied
Biosystems) or GlobalFiler1
PCR Amplification Kit (Applied
Biosystems). Y-STRs were analyzed using AmpF‘STR1
Yfiler1
PCR Amplification Kit (Applied Biosystems). Analysis of X-STR
markers including alternative amelogenin marker was done using
Mentype1
Argus X-8 Kit (Biotype, Germany).
To confirm the gender of the studied samples, a sex-
determining region Y (SRY) specific to males, was amplified. SRY
locus was investigated using the real-time PCR-based DNA
quantification kit Quantifiler1
Y Human Male DNA Quantification
Kit (Applied Biosystems).
DNA isolation and PCR amplification of above-mentioned
groups of markers including amelogenin and SRY genes were
performed according to manufacturer’s recommendations. PCR
amplifications were carried out on the GeneAmp PCR System 2700
(Applied Biosystems) and amplification products were separated
by capillary electrophoresis on the ABI PRISM1
3130xl Genetic
Analyzer, ABI PRISM1
3100 Genetic Analyzer and ABI PRISM1
3500 Genetic Analyzer (Applied Biosystems, Foster City, CA).
Fragments were automatically analyzed using GeneMapper ID-X
v.1.1.1 Software (Applied Biosystems). For the quantification of
the SRY gene expression ABI PRISM1
7000 Sequence Detection
System was used.
3. Results
A total of 11 cases with amelogenin abnormalities have
been detected in Belarusian males: 9 AMELY null and 2 AMELX
null cases. The results of autosomal STRs and amelogenin, Y-STRs,
X-STRs (including amelogenin locus) genotyping for all cases are
shown in the Supplementary Tables S1–S3, respectively.
3.1. Interstitial Yp11.2 deletion (AMELY-DYS458)
The AMELY-DYS458 deletion pattern has been identified in
4 out of 9 AMELY-negative cases (Table 1). Two cases (samples S2.1
and S2.2, S4.1 and S4.2) involve related males (father–son sample
Table 1
Results of gender identification in cases with amelogenin abnormalities.
Sample Phenotype AMEL (Identifiler Plus1
Kit) SRY Yfiler1
Kit (16 loci) Mentype1
Argus X-8 kit
Amplified Not amplified AMEL X/Y Number of X-chromosomes
Deletion AMELY-DYS458
S1 Male M/– + 15 loci 1 locus (DYS458) n.a. n.a.
S2.1 (father) Male M/– + 15 loci 1 locus (DYS458) M/– One X-chromosome
S2.2 (son) Male M/– + 15 loci 1 locus (DYS458) M/– One X-chromosome
S3 Male M/– + 15 loci 1 locus (DYS458) n.a. n.a.
S4.1 (Father) Male M/–
GlobalFiler X/–
+ 15 loci 1 locus (DYS458) n.a. n.a.
S4.2 (son) Male M/– + 15 loci 1 locus (DYS458) n.a. n.a.
XX-male, Y short arm inversion and translocation
S5 Male M/– + 4 loci (DYS456, DYS458, DYS19, DYS393) 12 loci M/– Heterozygous at 7 loci
S6 Male M/– + 4 loci (DYS456, DYS458, DYS19, DYS393) 12 loci n.a. n.a.
XX-male, Y short arm translocation
S7 Male M/– + 2 loci (DYS456, DYS393) 14 loci M/À Heterozygous at 7 loci
Mutation in primer-binding site
S8 Male M/– + All 16 loci – n.a. n.a.
S9 Male –/I n.a. n.a. n.a. M/I Hemizygous at 8 loci
S10 Male –/I n.a. n.a. n.a. n.a. n.a.
S11 Male M/– n.a. All 16 loci n.a. n.a. n.a.
n.a., not available; –, no alleles present (null).
S. Borovko et al. / Forensic Science International: Genetics 15 (2015) 98–104 99
3. pairs). The rest of the cases (S1 and S3) were crime scene samples
from unrelated males. In all 4 cases absence of AMELY was
detected with Identifiler1
Plus Kit. In the case S4.1 (our recent
expertise when GlobalFiler1
Kit was available) absence of AMELY
was confirmed with GlobalFiler1
Kit. It is interesting to note that
the GlobalFiler1
Kit helped to identify the sex of S4.1 sample
correctly as AMELY dropout was detected in this sample with
Identifiler1
Plus Kit (Supplementary Fig. S1).
Among 16 Y-STRs amplified with Yfiler1
Kit amplification of
only DYS458 marker was failed in the cases S1–S4 (Fig. 1). All cases
were SRY positive (data not shown). Thus, the complete absence of
AMELY and DYS458 and the presence of SRY gene in all 4 cases let
Fig. 1. Y-STRs haplotype of S2.1. In the case S2.1 amplification of only DYS458 was failed. The rest of Y-STR markers were successfully amplified with Yfiler1
Kit.
Fig. 2. Y-STRs haplotype of S5. Lack of amplification of the most of Yfiler1
Kit loci was observed in S5 except for DYS456, DYS458, DYS19 and DYS393.
S. Borovko et al. / Forensic Science International: Genetics 15 (2015) 98–104100
4. us to conclude that AMELY dropout in the cases S1–S4 was caused
by a deletion in the short arm of Y-chromosome (Yp11.2 region).
In addition, for the samples S2.1 and S2.2 (a father–son sample
pair) amelogenin and X-STRs were typed with Mentype1
Argus X-
8 Kit. The results of genotyping confirmed the absence of AMELY
and the presence of one X-chromosome in the samples. The DNA-
samples were hemizygous at all 8 X-STR loci.
3.2. SRY-positive XX male syndrome
We have identified 3 AMELY-negative samples with XX male
syndrome–samples S5, S6 and S7 (Table 1). Karyotyping was not
done for these samples. Therefore, we can only assume their XX
status. Interestingly, all three samples were SRY-positive (data not
shown).
Samples S5 and S6 were amplified successfully for two distal Yp
STR markers, DYS393 and DYS456, and two proximal Yp STR
markers, DYS458 and DYS19, to the absent AMELY. AMELY and
12 Y-STRs mapping to the long arm of Y-chromosome were
undetectable in the samples (Fig. 2). Absence of AMELY in sample
S5 was proved with Mentype1
Argus X-8 Kit. Moreover, S5 showed
heterozygous profile at 7 out of 8 X-STR markers, indicating the
presence of two X-chromosomes in S5 (Fig. 3). X-STR analysis was
not done for sample S6.
Sample S7 was another XX man and showed a different Y-STRs
pattern compared to the samples S5 and S6. Only DYS393 and
DYS456 loci were detected with Yfiler1
Kit in S7 (Fig. 4). SRY was
also identified in S7 (data not shown). These data pinpoint to the
presence of the deletion in S7, encompassing the major part of Y-
chromosome from Yp11.2 up to the whole long arm. Profiling with
Mentype1
Argus X-8 Kit confirmed the absence of AMELY in S7 and
revealed the heterozygous genotype of S7 at 7 out of 8 X-STR
markers (Supplementary Fig. S2). Thus, these findings support our
assumption that the man, from whom DNA sample S7 was
obtained, has a SRY-positive XX male syndrome.
3.3. Mutations in the primer-binding site of AMELX or AMELY alleles
Samples S8 and S11 were detected as AMELY-negative samples
with Identifiler1
Plus Kit. However, these samples showed
complete Y-STR profiles of the Yfiler1
Kit (Table 1). This data
let us to assume that AMELY dropout observed in S8 and S11 is
caused by a mutation occurred in the primer-binding region of the
AMELY allele.
Fig. 3. X-STR marker profiles of S5. AMELY null allele was detected in S5 with Mentype1
Argus X-8 Kit. Heterozygous profiles were observed at all X-STR loci in S5 except for
DXS8378 indicating the presence of two X-chromosomes in S5.
Fig. 4. Y-STRs haplotype of S7. Only two Y-STR loci DYS456 and DYS393 were amplified in S7 with Yfiler1
Kit.
S. Borovko et al. / Forensic Science International: Genetics 15 (2015) 98–104 101
5. Loss of AMELX has been detected in two male samples S9 and
S10 with Identifiler1
Plus Kit (Table 1). Amelogenin amplifica-
tion performed with another kit (Mentype1
Argus X-8) revealed
both AMELX and AMELY fragments in sample S9 (Fig. 5).
Moreover, sample S9 showed hemizygous X-STR profile with
only one allele at each X-STR locus. These findings support the
assumption of the presence of X-chromosome with a primer-
binding site mutation at the amelogenin locus in sample S9.
Genetic nature of AMELX dropout observed in sample S10 needs
to be further investigated as there is only data of amplification
with Identifiler1
Plus for this sample. Absence of AMELX in
S10 can be caused by either a primer-binding site mutation at
the amelogenin locus or a deletion of the amelogenin locus of
X-chromosome.
4. Discussion
In the present study, to our knowledge, we first reported cases
of amelogenin abnormalities in Belarusian population. Herein, 11
cases of amelogenin abnormalities collected during 15-year
practice in forensic DNA analysis in Belarus were described.
Genetic mechanisms underlying AMELX or AMELY dropouts
identified in these cases fall into four categories: (1) deletion
involving AMELY and DYS458 loci (n = 4), (2) loss of the long arm of
the Y-chromosome with partial X–Y translocation in an XX-man
(n = 2), (3) loss of most of the Y-chromosome in an XX man (n = 1),
(4) mutation in the primer-binding region of AMELX (n = 2) or
AMELY (n = 2) loci.
Deletions in Yp11.2 region are the major cause of the failure
of AMELY allele amplification [5,8,12]. AMELY dropout is often
combined with deletion of the DYS458 locus [7–9,11,12]. On
the other hand, the DYS458 null allele may serve as a strong
indicator of the AMELY-negative sample. High frequency of the
AMELY-DYS458 deletion pattern may be explained by small
physical distance (1.19 Mb) between these two loci [5,7–9].
Absence of AMELY and DYS458 amplification caused by Yp11.2
deletion has been detected in various populations with different
frequency (Table 2). It can be explained by population-specific
differences and by different sizes of analyzed population groups
reported in the papers [7,21]. The high percent of AMELY and
DYS458 null alleles have been identified in Nepalese males and
Malaysian Indians (a migrant male group from India) (Table 2). At
the same time AMELY and DYS458 null alleles have not been
detected in Malaysian Chinese. In the present study, we detected
4 cases with AMELY-DYS458 allelic pattern out of 11 cases of
amelogenin-negative Belarusian males (Table 2).
Large Yp11.2 deletion patterns DYS456-AMELY-DYS458 or
AMELY-DYS458-DYS19 have been identified in AMELY-negative
males in several studies [7,8,10]. We have not identified such
deletion patterns in AMELY-negative Belarusian males. In all 9
AMELY-negative cases Y-STR markers DYS456 and DYS19 were
successfully amplified with Yfiler1
Kit (Supplementary Table S2).
Overall, the frequency of AMELY dropout in Sri Lankan (2/24,
8.333%) [22], Nepalese (9/200, 4.50%) [2], (5/77, 6.490%) [6], and
Indian (10/4257, 0.230%) [23], (1/100, 1%) [9], (5/270, 1.852%) [24]
populations is notably higher than that observed in some
Caucasian population groups from Austria (5/28,182, 0.018%)
[21], Israel (1/96, 1.042%) [25], Spain (1/1000, 0.1%) [9], (1/768,
0.130%) [26], England (2/2000, 0.1%) [9], and Italy (1/13,000,
0.008%) [27]. The data on the frequency of either AMELY dropout or
AMELY-DYS458 deletion pattern in the Belarusian population
cannot be directly compared to that of above-mentioned Caucasian
population groups on the several reasons: (1) there are no data of
DYS458 marker amplification because this Y-STR marker was not
used in typing of the samples [21,25–27]; (2) different amount of
samples analyzed in the studies.
Fig. 5. Genetic profiles of autosomal STRs, X-STRs and amelogenin of S9 generated with Identifiler1
Plus (panels A and B) and Mentype1
Argus X-8 (panels C and D) Kits.
Absence of AMELX allele and presence of 112 bp fragment from AMELY was detected in S9 with Identifiler1
Plus Kit (panel B). Use of the alternative set of primers for
amelogenin included in Mentype1
Argus X-8 Kit let to detect both AMELX (103 bp) and AMELY (109 bp) fragments in S9 (panel C). S9 was hemizygous for all 8 X-STR loci
included in Mentype1
Argus X-8 Kit (panels C and D).
S. Borovko et al. / Forensic Science International: Genetics 15 (2015) 98–104102
6. Paternity testing samples S2.1 and S2.2, S4.1 and S4.2 were
collected from related men (father–son sample pairs). It means
that the deletion AMELY-DYS458 identified in these samples is not
a de novo mutation, but was transmitted from the father to
the son. Therefore, the deletion in the short arm of the
Y-chromosome Yp11.2, containing AMELY and DYS458 loci, did
not affect fertility as paternity was proven in both cases S2
and S4. Similar observations have been done by several authors
[2,7,8,11,12,27,28]. Deletions in the long arm of the Y-chromosome
are associated with azoospermia and can cause reproduction
failure in males [1,9,16,27,29,30].
Combined use of different kits for analysis of autosomal STRs,
Y-STRs, X-STRs and amelogenin and SRY genes let us to identify
three cases with SRY-positive XX-male syndrome: S5, S6, and S7.
We could not perform karyotype analysis for these samples.
However, with Mentype1
Argus X-8 Kit samples S5 and S7
exhibited a heterozygous profile with two alleles at 7 out of 8
X-STR loci. This finding confirms the presence of two X-
chromosomes in samples S5 and S7. Although the X-STR analysis
was not done for sample S6, we combined samples S5 and S6 in
one group because of the similar genetic findings in Y-STR typing
in the samples.
Long arm loss of Y-chromosome has been detected in the
AMELY-negative samples S5 and S6. Only four Y-STR markers,
DYS393, DYS456, DYS458, and DYS19, could be amplified in these
samples. In addition, heterozygous profile at 7 out of 8 analyzed X-
STR loci has been identified in sample S5. SRY has been detected in
both S5 and S6 samples. Cases with similar genetic findings have
been described in several studies [7,31]. It has been proposed a
putative genetic mechanism explaining the discrepant pattern
observed in the above-mentioned samples: DYS19 is transferred to
the distal IR3 element (inverted repeats region) by a paracentric
inversion, followed by the translocation of the terminal segment of
Y-chromosome, including SRY, DYS393, DYS456, DYS19, and
DYS458, onto the X-chromosome [7,31].
A case with loss of most of Y-chromosome in a man with
XX male syndrome similar to S7 (current study) was described
by Ma et al. [7]. Two out of 16 Y-STR loci, DYS393 and DYS456,
were amplified in S7. Ma and coauthors proposed a genetic
model explaining mechanism underlying deletion pattern
observed in these samples: AMELY together with the Yp markers,
DYS458, DYS19, and the whole long arm of Y-chromosome
undergo deletion, while the distal Yp markers, including SRY,
DYS393, and DYS456, are translocated onto the short arm of
X-chromosome [7].
A plausible explanation for AMELY or AMELX dropout in four
samples, S8, S9, S10, S11, can be a mutation in primer-binding
region of AMELY (samples S8 and S11) or AMELX (samples S9 and
S10).
Successful amplification of all 16 Y-STR loci in the AMELY-
negative samples S8 and S11 suggested that AMELY dropout in
these samples resulted from the point mutation in the primer-
binding site of AMELY. AMELY null allele was detected in S8 with
Identifiler1
Plus Kit. Since different kit (e.g. GlobalFiler1
or
Mentype1
Argus X-8 Kits) might use different pair of primers for
AMELY allele, this sort of amelogenin abnormalities may not
appear in other PCR kits.
AMELX locus that was not detected in S9 with Identifiler1
Plus Kit was successfully identified with Mentype1
Argus X-8
Kit. In addition, sample S9 showed a hemizygous profile at all
eight X-STR loci. These data point towards the presence of
primer-binding site mutation at AMELX locus. Zehethofer
and Rolf described similar genetic findings for a pair of samples
from paternity testing group (farther-son) [14]. AMELX allele
dropouts are believed to be mainly caused by mutations in
the primer-binding region [5]. Moreover, the loss of AMELX
Table 2
Frequency distribution of males with AMELY-DYS458 deletion pattern in different populations.
Population Null AMELY-DYS458/
null AMELY
No. of males
studied
Source of the samples Population
frequency
Frequency (number
of null AMELY)
Reference
Nepalese 9/9 200 Paternity testing group
(n = 200)
9/200 (4.5%) – [2]
Malaysian Chinese 0 331 Y-STR database and forensic
casework groups (n = 980)
– – [9]
Malaysian Indiansa
10/12 315 10/315 (3.175%) –
Malaysian Malaysa
2/12 334 2/334 (0.599%) –
Chineseb
2/3 8087 DNA database (n = 8087) 2/8087 (0.025%) – [10]
(Guangdong province)
Chinesec
3/3 40 DNA database (n = 12,891) 3/12,891 (0.023%) – [8]
(Zheijiang and
Guangdong provinces)
Chinesed
13/18 79,304 DNA database and forensic
casework groups (n = 79,304)
13/79,304 (0.016%) – [7]
(North of China)
Mixed population
groupe
9/45 45 Paternity testing group,
population studies
9/45 (20%) – [1]
Japanese 4/4 4 Forensic casework – 4/4 (100%) [11]
Italian 2/2 2 Paternity testing group – 2/2 (100%) [12]
Belarusian 4/9 13 Forensic casework, paternity
testing groups
– 4/9 (44.4%) Current study
a
In all samples with AMELY-DYS458 deletion pattern, the absence of Y-specific MSY1 minisatellite located between AMELY and DYS458 loci was found.
b
One sample showed AMELY-DYS458 deletion pattern, another one showed DYS456-AMELY-DYS458 deletion pattern.
c
Two samples showed AMELY-DYS458 deletion pattern, one sample showed DYS456-AMELY-DYS458 deletion pattern.
d
AMELY-DYS458 deletion pattern was identified in 8 out of 18 AMELY-negative samples. Different deletion patterns including the locus DYS458 were detected in 5
samples with AMELY dropout: DYS456-AMELY-DYS458 null alleles (1 sample); AMELY-DYS458-DYS19 null alleles (1 sample); AMELY-DYS458-GATA_H4 deletion
(2 samples); deletion involving the major part of Y-chromosome except for two Y-STRs DYS456 and DYS393 (1 sample).
e
Mixed population group comprises 45 AMELY-deficient males from 12 populations.
S. Borovko et al. / Forensic Science International: Genetics 15 (2015) 98–104 103
7. allele is more common in some populations [5]. AMELX dropouts
have been detected in Polish population (1/5534, 0.018%) [17],
males from West Africa (10/503, 2%) [18], and African–American
males (48/144,391, 0.033%) [5].
In summary, our data indicate that the combined use of
different kits such as Identifiler1
Plus or GlobalFiler1
for
autosomal STR loci and amelogenin, Quantifiler1
Y for SRY gene,
Yfiler1
for Y-profiling and Mentype1
Argus X-8 or Investigator1
Argus X-12 for X-STRs and amelogenin may help to overcome
problems related to the wrong gender determination and to
elucidate the genetic mechanisms underlying amelogenin abnor-
malities. A new PCR multiplex GenderPlex presented by Esteve et
al. [32] gives additional possibilities for a forensic DNA expert to
avoid sex misinterpretation.
The data on the incidence of amelogenin abnormalities in the
global population are scarce. Therefore, we believe that the data
presented in current study along with planned study on the
frequency of AMELY and AMELX dropouts in Belarusian population
would be helpful for forensic community.
Conflict of interest
The authors declare that they have no conflict of interest.
Funding
The study was not funded by a special source.
Acknowledgement
We would like to thank all members of DNA laboratory of State
Medical Forensic Service of the Republic of Belarus.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.fsigen.2014.10.014.
References
[1] M.A. Jobling, I.C. Lo, D.J. Turner, G.R. Bowden, A.C. Lee, Y. Xue, D. Carvalho-Silva,
M.E. Hurles, S.M. Adams, Y.M. Chang, T. Kraaijenbrink, J. Henke, G. Guanti, B.
McKeown, R.A. van Oorschot, R.J. Mitchell, P. de Knijff, C. Tyler-Smith, E.J. Parkin,
Structural variation on the short arm of the human Y chromosome: recurrent
multigene deletions encompassing Amelogenin Y, Hum. Mol. Genet. 16 (2007)
307–316, http://dx.doi.org/10.1093/hmg/ddl465.
[2] D.K. Jha, J.Pd. Rijal, N.T. Chhetri, Nepalese null AMELY males and their y-haplo-
types, Sci. World 8 (2010) 97–101, 10.3126/sw.v8 i8.3858.
[3] K.M. Sullivan, A. Mannucci, C.P. Kimpton, P. Gill, A rapid and quantitative DNA sex
test: fluorescence-based PCR analysis of XY homologous gene amelogenin, Bio-
techniques 15 (1993) 636–638, 640–641.
[4] A. Mannucci, K.M. Sullivan, P.L. Ivanov, P. Gill, Forensic application of a rapid
quantitative DNA sex test by amplification of the X–Y homologous gene amplifi-
cation, Int. J. Legal Med. 106 (1994) 190–193, http://dx.doi.org/10.1007/
BF01371335.
[5] J. Butler, Advanced Topics in Forensic DNA Typing: Methodology, Acad. Press,
2011, pp. 130–132.
[6] A.M. Cadenas, M. Regueiro, T. Gayden, N. Singh, L.A. Zhivotovsky, P.A. Underhill,
R.J. Herrera, Male amelogenin dropouts: phylogenetic context, origins and impli-
cations, Forensic Sci. Int. 166 (2007) 155–163, http://dx.doi.org/10.1016/j.
forsciint.2006.05.002.
[7] Y. Ma, J.Z. Kuang, J. Zhang, G.M. Wang, Y.J. Wang, W.M. Jin, Y.P. Hou, Y chromo-
some interstitial deletion induced Y-STR allele dropout in AMELY-negative indi-
viduals, Int. J. Legal Med. 126 (2012) 713–724, http://dx.doi.org/10.1007/s00414-
012-0720-8.
[8] W. Chen, W. Wu, J. Cheng, Y. Zhang, Y. Chen, H. Sun, Detection of the deletion
on Yp11.2 in a Chinese population, Forensic Sci. Int. Genet. 8 (2014) 73–79, http://
dx.doi.org/10.1016/j.fsigen.2013.07.003.
[9] Y.M. Chang, R. Perumal, P.Y. Keat, R.Y.Y. Yong, D.L. Kuehn, L. Burgoyne, A distinct
Y-STR haplotype for amelogenin negative males characterised by a large Yp11.2
(DYS458-MSY1-AMEL-Y) deletion, Forensic Sci. Int. 166 (2007) 115–120, http://
dx.doi.org/10.1016/j.forsciint.2006.04.013.
[10] X. Ou, W. Chen, H. Chen, F. Zhao, J. Zheng, D. Tong, Y. Chen, A. Chen, H. Sun, Null
alleles of the X and Y chromosomal amelogenin gene in a Chinese population, Int.
J. Legal Med. 126 (2012) 513–518, http://dx.doi.org/10.1007/s00414-011-0594-1.
[11] R. Kumagai, Y. Sasaki, T. Tokuta, H. Biwasaka, Y. Aoki, DNA analysis of family
members with deletion in Yp11.2 region containing amelogenin locus, Leg. Med.
10 (2008) 39–42, http://dx.doi.org/10.1016/j.legalmed.2007.05.009.
[12] S. Turrina, G. Filippini, D. De Leo, Evaluation of deleted region from Yp11.2 of two
amelogenin negative related males, Forensic Sci. Int. Genet. Suppl. Ser. 2 (2009)
240–241, http://dx.doi.org/10.1016/j.fsigss.2009.08.157.
[13] A. Sharp, K. Kusz, J. Jaruzelska, W. Tapper, M. Szarras-Czapnik, J. Wolski, P. Jacobs,
Variability of sexual phenotype in 46,XX(SRY+) patients: the influence of spread-
ing X inactivation versus position effects, J. Med. Genet. 42 (2005) 420–427,
http://dx.doi.org/10.1136/jmg.2004.022053.
[14] K. Zehethofer, B. Rolf, A molecular analysis of three amelogenin negative males
in two routine paternity tests, Forensic Sci. Int. Genet. 5 (2011) 550–551, http://
dx.doi.org/10.1016/j.fsigen.2010.04.006.
[15] A. de la Chapelle, H. Hortling, M. Niemi, J. Wennstroem, XX sex chromosomes in a
human male. First case, Acta Med. Scand. 175 (1964) 25–28.
[16] E. Vorona, M. Zitzmann, J. Gromoll, A.N. Schu¨ring, E. Nieschlag, Clinical, endo-
crinological, and epigenetic features of the 46 XX male syndrome, compared with
47,XXY Klinefelter patients, J. Clin. Endocrinol. Metab. 92 (2007) 3458–3465,
http://dx.doi.org/10.1210/jc.2007-0447.
[17] A. Maciejewska, R. Pawłowski, A rare mutation in the primer binding region of the
Amelogenin X homologue gene, Forensic Sci. Int. Genet. 3 (2009) 265–267, http://
dx.doi.org/10.1016/j.fsigen.2009.01.010.
[18] C. Alves, M. Coelho, J. Rocha, A. Amorim, The Amelogenin locus displays a high
frequency of X homologue failures in Sa˜o Tome´ Island (West Africa), Int. Congr.
Ser. 1 (2006) 271–273, http://dx.doi.org/10.1016/j.ics.2005.10.036.
[19] J.G. Shewale, S.L. Richey, S.K. Sinha, Anomalous Amplification of the Amelogenin
Locus Typed by AmpFLSTR1
Profiler PlusTM
Amplification Kit, vol. 2, FSC, 2000
Available at http://www.fbi.gov/about-us/lab/forensic-science-communications/
fsc/oct2000/index.htm/shewale.htm.
[20] J. Sambrook, E.F. Fritsch, T. Maniatis, Molecular Cloning: A Laboratory Manual,
second ed., Cold Spring Harbor Laboratory Press, New York, 1989.
[21] M. Steinlechner, B. Berger, H. Niederstatter, W. Parson, Rare failures in the
amelogenin sex test, Int. J. Legal Med. 116 (2002) 117–120, http://dx.doi.org/
10.1007/s00414-001-0264-9.
[22] F.R. Santos, A. Pandya, C. Tyler-Smith, Reliability of DNA-based sex tests, Nat.
Genet. 18 (1998) 103, http://dx.doi.org/10.1038/ng0298-103.
[23] V.K. Kashyap, S. Sahoo, T. Sitalaximi, R. Trivedi, Deletions in the Y-derived
amelogenin gene fragment in the Indian population, BMC Med. Genet. 7
(2006) 37–43, http://dx.doi.org/10.1186/1471-2350-7-37.
[24] K. Thangaraj, A.G. Reddy, L. Singh, Is the amelogenin gene reliable for gender
identification in forensic casework and prenatal diagnosis? Int. J. Legal Med. 116
(2002) 121–123, http://dx.doi.org/10.1007/s00414-001-0262-y.
[25] A. Michael, P. Brauner, Erroneous gender identification by the amelogenin sex
test, J. Forensic Sci. 49 (2004) 258–259.
[26] E. Bosch, A.C. Lee, F. Calafell, E. Arroyo, P. Henneman, P. de Knijff, M.A. Jobling,
High resolution Y chromosome typing: 19 STRs amplified in three multiplex
reactions, Forensic Sci. Int. 125 (2002) 42–51, http://dx.doi.org/10.1016/S0379-
0738(01)00627-2.
[27] W. Lattanzi, M. Di Giacomo, G.M. Lenato, G. Chimienti, G. Voglino, A large
interstitial deletion encompassing the amelogenin gene on the short arm of
the Y chromosome, Hum. Genet. 116 (2005) 395–401, http://dx.doi.org/
10.1007/s00439-004-1238-z.
[28] I. Ferreira, Sequence Variation of the Amelogenin Gene on the Y-chromosome,
Thesis submitted for the degree Philosophiae Doctor (Ph.D.) in Biochemistry
at the North-West University (Potchefstroom Campus), November 2010,
http://hdl.handle.net/10394/4412.
[29] P. Yen, The fragility of fertility, Nat. Genet. 29 (2001) 243–244, http://dx.doi.org/
10.1038/ng1101-243.
[30] D.J. Ballard, C. Phillips, G. Wright, C.R. Thacker, C. Robson, A.P. Revoir, D. Syn-
dercombe Court, A study of mutation rates and the characterisation of interme-
diate, null and duplicated alleles for 13 Y chromosome STRs, Forensic Sci. Int.
155 (2005) 65–70, http://dx.doi.org/10.1016/j.forsciint.2004.12.012.
[31] P. Balaresque, E.J. Parkin, L. Roewer, D.R. Carvalho-Silva, R.J. Mitchell, R.A. van
Oorschot, J. Henke, M. Stoneking, I. Nasidze, J. Wetton, P. de Knijff, C. Tyler-Smith,
M.A. Jobling, Genomic complexity of the Y-STR DYS19: inversions, deletions
and founder lineagescarrying duplications, Int. J. Leg. Med. 123 (2009) 15–23,
http://dx.doi.org/10.1007/s00414-008-0253-3.
[32] C.A. Esteve, H. Niederstatter, W. Parson, ‘‘GenderPlex’’ a PCR multiplex for reliable
gender determination of degraded human DNA samples and complex gender
constellations, Int. J. Legal Med. 123 (2009) 459–464, http://dx.doi.org/10.1007/
s00414-008-0301.
S. Borovko et al. / Forensic Science International: Genetics 15 (2015) 98–104104