This document discusses different types of genetic disorders including single gene disorders, chromosomal disorders, and multifactorial disorders. It focuses on single gene disorders which can be autosomal dominant, autosomal recessive, or X-linked. Autosomal dominant disorders affect both males and females and there is a 50% chance of passing the disorder to offspring. Autosomal recessive disorders do not usually affect the parents but there is a 25% chance of siblings being affected. Examples of autosomal recessive disorders provided are sickle cell disease, cystic fibrosis, and Tay-Sachs disease. X-linked disorders mainly affect males and are more likely to be passed from mother to children than father to children.
This presentation is fetures the basic introduction to Genome mosaicism in humans and nature, with some examples of its harmful effects on humans, with
The modern scientific era begins with the work of Austrian monk, Gregor Mendel, who in 1865 presented the results of his breeding experiments on contrasting characters in garden peas
Mendel's laws of inheritance
Dominant inheritance
Dominant mutations are expressed when only one copy of that mutation is present. Therefore, anyone who inherits one dominant disease mutation such as the mutation for Huntington’s disease will have that disease.
Dominantly inherited genetic diseases tend to occur in every generation of a family. Each affected person usually has one affected parent.
However, dominant mutations can also happen in an individual for the first time, with no family history of the condition (spontaneous mutation).
Genetic epidemiology, classification of Genetic Disorder, factor causing gene...Mohan Bastola
Genetic epidemiology, classification of Genetic Disorder, factor causing genetic abnormalities, difference between congenital and teratogenic abnormalities and prevention of genetic diseases
Effects of Gene Mutation. 2Running Head EFFECTS OF GENE MUT.docxjack60216
Effects of Gene Mutation. 2
Running Head: EFFECTS OF GENE MUTATION
Effects of Gene Mutation
Name:
Institution:
Date:
Effects of Gene Mutation
What are the effects of gene mutation and its future in humanity?
Mutations are visible changes in chromosomes as well as genes. The process of mutation can happen within the cell or be transmitted from one cell to another in a multicellular organism. Rates of mutation differ from one organism to another, from one place to another, time to time and from one gene to another. DNA genes are frequently changing; mutation can be seen as accidental changes that leads to malformed proteins hence disease. Our lives begin with mutations inherited from the parents. The inherited gene mutation is germ-line mutations. Some mutations can be harmful while some beneficial. With time, genetic mutation brings about diversity which in turn sustains populations healthy. There are also silent mutations which have no effects (Adeniran, 2014).
Presence of DNA in our body cells provides a place for mutation to take place. But r, some of these transformations can fail to be transmitted to the offspring and fail to be considered for evolution. This condition is described as somatic mutation. Many times mutation is seen as insignificant cause of genetic ailment. As they display undesirable effects, contrary to many expectations, some mutations can have positive effects (U E, n.d).
A number of organisms have strong regulating genes that assist in determining how the body is laid off. A case in point is Hox genes which are common among animals that designate the direction of the head at the same time determining the place for appendages. To this extend therefore the transformation in primary body layout may not be avoided; instead it may need transformation in Hox gene and promote the natural selection (U E, n.d).
What remain common in most of the people are the harmful mutations that cause diseases. Cystic fibrosis and sickle cell anemia among other genes are examples of inherited gene disorders. These inherited genetic diseases in most cases are recessive and they exist in pairs (Adeniran, 2014).
Scientists approximate that a very human being has about 5-10 prospective deadly mutations. In most cases cancer is the resultant of these series mutations in a cell. In most cases this problem is as a result of p53 gene that brings the mutated cells to a standstill (Adeniran, 2014).
Categorization of Gene Mutations
A gene mutation is an eternal change in DNA arrangement making up a gene. This arrangement varies from majority of persons, ranging from DNA building block and gene size. Mutation of genes can be categorized into two: First is the hereditary mutation which is inheritable from the parent of child. Germ line mutations are responsible for these hereditary mutations, because of their presence in the parent sperm or egg cells (Harten, 1998).
Second is Acquired mutations which occurs specifically at some po ...
This presentation is fetures the basic introduction to Genome mosaicism in humans and nature, with some examples of its harmful effects on humans, with
The modern scientific era begins with the work of Austrian monk, Gregor Mendel, who in 1865 presented the results of his breeding experiments on contrasting characters in garden peas
Mendel's laws of inheritance
Dominant inheritance
Dominant mutations are expressed when only one copy of that mutation is present. Therefore, anyone who inherits one dominant disease mutation such as the mutation for Huntington’s disease will have that disease.
Dominantly inherited genetic diseases tend to occur in every generation of a family. Each affected person usually has one affected parent.
However, dominant mutations can also happen in an individual for the first time, with no family history of the condition (spontaneous mutation).
Genetic epidemiology, classification of Genetic Disorder, factor causing gene...Mohan Bastola
Genetic epidemiology, classification of Genetic Disorder, factor causing genetic abnormalities, difference between congenital and teratogenic abnormalities and prevention of genetic diseases
Effects of Gene Mutation. 2Running Head EFFECTS OF GENE MUT.docxjack60216
Effects of Gene Mutation. 2
Running Head: EFFECTS OF GENE MUTATION
Effects of Gene Mutation
Name:
Institution:
Date:
Effects of Gene Mutation
What are the effects of gene mutation and its future in humanity?
Mutations are visible changes in chromosomes as well as genes. The process of mutation can happen within the cell or be transmitted from one cell to another in a multicellular organism. Rates of mutation differ from one organism to another, from one place to another, time to time and from one gene to another. DNA genes are frequently changing; mutation can be seen as accidental changes that leads to malformed proteins hence disease. Our lives begin with mutations inherited from the parents. The inherited gene mutation is germ-line mutations. Some mutations can be harmful while some beneficial. With time, genetic mutation brings about diversity which in turn sustains populations healthy. There are also silent mutations which have no effects (Adeniran, 2014).
Presence of DNA in our body cells provides a place for mutation to take place. But r, some of these transformations can fail to be transmitted to the offspring and fail to be considered for evolution. This condition is described as somatic mutation. Many times mutation is seen as insignificant cause of genetic ailment. As they display undesirable effects, contrary to many expectations, some mutations can have positive effects (U E, n.d).
A number of organisms have strong regulating genes that assist in determining how the body is laid off. A case in point is Hox genes which are common among animals that designate the direction of the head at the same time determining the place for appendages. To this extend therefore the transformation in primary body layout may not be avoided; instead it may need transformation in Hox gene and promote the natural selection (U E, n.d).
What remain common in most of the people are the harmful mutations that cause diseases. Cystic fibrosis and sickle cell anemia among other genes are examples of inherited gene disorders. These inherited genetic diseases in most cases are recessive and they exist in pairs (Adeniran, 2014).
Scientists approximate that a very human being has about 5-10 prospective deadly mutations. In most cases cancer is the resultant of these series mutations in a cell. In most cases this problem is as a result of p53 gene that brings the mutated cells to a standstill (Adeniran, 2014).
Categorization of Gene Mutations
A gene mutation is an eternal change in DNA arrangement making up a gene. This arrangement varies from majority of persons, ranging from DNA building block and gene size. Mutation of genes can be categorized into two: First is the hereditary mutation which is inheritable from the parent of child. Germ line mutations are responsible for these hereditary mutations, because of their presence in the parent sperm or egg cells (Harten, 1998).
Second is Acquired mutations which occurs specifically at some po ...
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
2. INTRODUCTION
•A genetic disorder is an illness caused by one or more
abnormalities in the genome, especially a condition that is
present from birth (congenital).
•Most genetic disorders are quite rare and affect one person
in every several thousands or millions.
•Genetic disorders may or may not be heritable, i.e., passed
down from the parents' genes.
4. SINGLE-GENE DISORDERS
• Mutations involving single genes typically follow one
of three patterns of inheritance:
autosomal dominant,
autosomal recessive,
X-linked.
5. AUTOSOMAL DOMINANT DISORDERS
• Are manifested in the heterozygous state, so at least one parent of an
index case is usually affected;
• Both males and females are affected, and both can transmit the
condition.
• When an affected person marries an unaffected one, every child has one
chance in two of having the disease.
• In this condition normal people have genotype d/d, affected
individual with mild disease have D/d and severely affected have
D/D which is often lethal. Most of those who survive are
6.
7. In addition to these basic rules, autosomal dominant conditions are
characterized by the following:
i) With every autosomal dominant disorder, some proportion of patients do not
have affected parents. Such patients owe their disorder to new mutations
involving either the egg or the sperm from which they were derived.
• Their siblings are neither affected nor at increased risk for disease
development.
• The proportion of patients who develop the disease as a result of a new
mutation is related to the effect of the disease on reproductive capability.
• If a disease markedly reduces reproductive fitness, most cases would be
expected to result from new mutations.
• Many new mutations seem to occur in germ cells of relatively older fathers.
8. ii)Clinical features can be modified by variations in penetrance
and expressivity.
• Some individuals inherit the mutant gene but are
phenotypically normal. This is referred to as incomplete
penetrance. Penetrance is expressed in mathematical terms.
Thus, 50% penetrance indicates that 50% of those who carry
the gene express the trait.
• In contrast to penetrance, if a trait is seen in all individuals
carrying the mutant gene but is expressed differently among
individuals, the phenomenon is called variable expressivity.
iii) In many conditions the age at onset is delayed; symptoms
and signs may not appear until adulthood (as in Huntington
disease).
9. The biochemical mechanisms of autosomal
dominant disorders
• Depends upon the nature of the mutation and the type of
protein affected.
• Most mutations lead to the reduced production of a gene
product or give rise to a dysfunctional or inactive protein.
• Whether such a mutation gives rise to dominant or recessive
disease depends on whether the remaining copy of the gene
is capable of compensating for the loss.
• Thus, understanding the reasons why particular loss-of-
function mutations give rise to dominant vs. recessive disease
patterns requires an understanding of the biology.
10. Many autosomal dominant diseases arising from
deleterious mutations fall into one of a few familiar
patterns:
• 1. Those involved in regulation of complex
metabolic pathways that are subject to feedback
inhibition. Membrane receptors such as the low-
density lipoprotein (LDL) receptor provide one
such example; in familial hypercholesterolemia,
discussed later, a 50% loss of LDL receptors
results in a secondary elevation of cholesterol
that, in turn, predisposes to atherosclerosis in
affected heterozygotes.
11. • 2. Key structural proteins, such as collagen and cytoskeletal
elements of the red cell membrane (e.g., spectrin). The
biochemical mechanisms by which a 50% reduction in the
amounts of such proteins results in an abnormal phenotype
are not fully understood.
• In some cases, especially when the gene encodes one
subunit of a multimeric protein, the product of the mutant
allele can interfere with the assembly of a functionally normal
multimer.
• Less common than loss-of-function mutations are gain of-
function mutations, which can take two forms.
12.
13. AUTOSOMAL RECESSIVE DISORDERS
• These make up the largest category of Mendelian disorders.
They occur when both alleles at a given gene locus are
mutated.
• These disorders are characterized by the following features:
(1) The trait does not usually affect the parents of the affected
individual, but siblings may show the disease; (2) siblings
have one chance in four of having the trait (i.e., the recurrence
risk is 25% for each birth); and (3) if the mutant gene occurs
with a low frequency in the population, there is a strong
likelihood that the affected individual (proband) is the product
of a consanguineous marriage.
• Autosomal recessive disorders include almost all inborn errors
14.
15. The following features generally apply to most autosomal
recessive disorders and distinguish them from autosomal
dominant diseases
• The expression of the defect tends to be more uniform than in
autosomal dominant disorders.
• Complete penetrance is common.
• Onset is frequently early in life.
• Although new mutations associated with recessive disorders do occur,
they are rarely detected clinically. Since the individual with a new
mutation is an asymptomatic heterozygote, several generations may
pass before the descendants of such a person mate with other
heterozygotes and produce affected offspring.
• Many of the mutated genes encode enzymes. In heterozygotes, equal
amounts of normal and defective enzyme are synthesized. Usually the
natural “margin of safety” ensures that cells with half the usual
complement of the enzyme function normally.
16.
17. Sickle cell
• Sickle cell disease is caused
by a mutation in the
hemoglobin-β gene found on
chromosome 11. This results
in a defective haemoglobin
(Hb).
• After giving up oxygen these
defective Hb molecules
cluster together resulting in
formation of rod like
structures
• The red blood cells become
18.
19. Other examples
• Individual with cystic fibrosis produce mucus that is
abnormally thick and sticky that can damage different organs
specially lungs resulting in chronic infections.
• Tay-Sachs disease is due to absence of an enzyme called
hexosaminidase A which results in a fatty substance
accumulation in nerve cells particularly affecting the brain. It is
a fatal disease manifest in childhood. One in 27 persons of
European Ashkenazi Jewish origin individuals carries the Tay-
Sachs gene.
• Phenylketonuria is caused by a mutation in phenylalanine
hydroxylase gene resulting in increase in phenylalanine in the
blood
20. X-Linked Disorders
•X-linked recessive inheritance accounts for a small
number of well-defined clinical conditions.
•All sex-linked disorders are X-linked, and almost all are
recessive
•Mutations on X x-some
•M more affected than F
•Chance of passing on the disorder differ btn men and
women
• Sons of an affected man will not be affected, daughters will
(no male-male transmission).
• For an affected woman, there will be a 50% chance for boys
and girls