Molecular Genetics and Genetic Disorders

Molecular Genetics & Genetic Disorders

• The lecture covers the molecular basis of genetics, including gene structure, function, and expression.
• It also details different types of mutations and their impact on human health.
• The classification and examples of genetic disorders, including molecular pathogenesis and inheritance patterns, are discussed.
• Various diagnostic techniques and molecular tools used in studying genetic disorders are introduced.

Activities

• Activities include the foundation of molecular genetics, molecular diagnostics, and emerging tools.
• Genetic disorders and chromosomal disorders will also be covered.
• Genetic disorders involving Mendelian inheritance will also be part of the activities.

Genetic Disorders Part 2

• Introduction to genetic disorders focuses on diseases caused by abnormalities in the genome.
• These abnormalities can involve single genes, multiple genes, chromosomes, or mitochondria.

Classification of Genetic Disorders

• Genetic disorders are classified into chromosomal disorders, single-gene disorders, polygenic disorders, and disorders with non-classic inheritance.

Pedigree Symbols

• Symbols represent individuals in family trees.
• Affected males are represented by filled squares.
• Unaffected males are represented by empty squares.
• Affected females are represented by filled circles.
• Unaffected females are represented by empty circles.

Single-Gene (Mendelian) Disorders

• Mutations in a single gene cause effects.
• Some mutations result in partial expression in heterozygotes and full expression in homozygotes.
• Traits are often dominant or recessive.
• Codominance is also possible in some cases (both alleles contribute to phenotype).
• Example traits like blood type (Ag) and HLA antigen.
• Inheritance patterns include autosomal dominant, autosomal recessive, and X-linked.
• Mutations can have multiple effects (pleiotropism).
• Different genetic loci may contribute to the same trait (genetic heterogeneity).

Mendelian Disorders

• Mutations in a single gene result in significant effects.
• Autosomal genes have partial expression (heterozygotes) and full expression (homozygotes).
• Traits can be dominant or recessive.
• Some cases involve codominance where both alleles contribute to the phenotype.
• For example, blood type or HLA antigens are codominant expressions.
• Pleiotropism is a single mutation causing multiple effects.
• Genetic heterogeneity demonstrates how multiple genetic locations can result in a similar trait.
• Environmental factors and compensatory genes can influence phenotype expression

Types of Mendelian Inheritance

• Autosomal Dominant: Affects males and females equally, typically with one affected parent having a 50% chance of passing the trait to offspring. Incomplete penetrance and variable expressivity are possible.
• Autosomal Recessive: Also affects males and females equally, requires two mutant alleles (homozygous) for expression. Typically asymptomatic carriers pass the trait to offspring.
• X-linked Recessive: Predominantly affects males lacking a compensating second X chromosome. Carrier females may have mild symptoms. Absent male-to-male transmission.

Estimated Prevalence of Mendelian Disorders

• A table provides prevalence estimates for various Mendelian disorders among newborns.

X-linked Disorders

• X-linked dominant traits affect both sexes, but females are more likely to survive. Affected males pass the trait to all daughters, but no sons.
• X-linked recessive traits predominantly affect males. Carrier females may experience mild symptoms.
• X-linked traits do not show male-to-male transmission.

Autosomal Dominant Disorders

• Includes disorders like Huntington's disease, neurofibromatosis, myotonic dystrophy, and polycystic kidney disease.
• Often caused by structural protein deficiencies and receptor/channel problems.
• Mutation in HTT gene causes expansion of CAG trinucleotide repeats.

Autosomal Recessive Disorders

• Examples include cystic fibrosis, phenylketonuria, sickle cell anemia, and various lysosomal storage disorders and thalassemias.
• Often due to protein enzyme, transport, or hemoglobin deficiencies.
• Usually manifest in early life

Mechanisms of Some Autosomal Dominant Disorders

• Mechanisms for some examples like neurofibromatosis (disrupting tumor suppressor proteins), familial polyposis coli (abnormal Wnt signaling), hereditary spherocytosis (weakening red blood cell membrane), and achondroplasia (inhibiting bone growth).

Marfan Syndrome

• Key features include eye problems, abnormal chest, heart, and lung problems, a short torso, tall/thin body frame, long arms, legs, and fingers.

Autosomal Recessive Inheritance (Pedigree)

• A diagram of a family tree illustrating inheritance of autosomal recessive traits.

X-linked Recessive Disorders

• Duchenne muscular dystrophy and hemophilia A and B are examples of X-linked recessive disorders.
• Characterized by varying degrees of severity, affecting males primarily.

X-Linked Recessive Disorders Mechanisms

• Includes mechanisms for disorders like hemophilia A (deficient clotting factor VIII), G6PD deficiency (reduced glucose-6-phosphate dehydrogenase), and Duchenne muscular dystrophy(progressive muscle degeneration).

Single-Gene Disorders With Non-Classic Inheritance

• These disorders fall into categories: trinucleotide repeat mutations; mitochondrial gene mutations; defective genomic imprinting; and disorders related to gonadal mosaicism.

Trinucleotide Repeat Mutations

• Mutations characterized by repeated short DNA sequences.
• Associated with disorders like Fragile X syndrome, Huntington's disease, and myotonic dystrophy.
• Often show a pattern of increasing severity with each successive generation.

Fragile X Syndrome

• Causes a form of familial mental retardation.
• Premutation CGG repeats in FMR1 gene on X chromosome.
• Hypermethylation of the FMR1 gene shuts down its transcription causing the disorder.

Mitochondrial Gene Mutations

• Inherited exclusively from the mother.
• Affect high-energy-requiring cells such as brain, muscles, and eyes.
• Leber hereditary optic neuropathy (LHON) is an example of mitochondrial disorder.

Defective Genomic Imprinting

• Certain genes expressed uniquely from either the mother or father.
• Inactivated gene is inactivated through Imprinting.
• Prader-Willi syndrome and Angelman syndrome result from impaired imprinting mechanisms.

Disorders Associated With Gonadal Mosaicism

• Mutations happen post-zygotically.
• Individual appears phenotypically normal, but carries the mutated gene and can pass it on to their offspring.
• Duchenne Muscular Dystrophy is an example of this.

This quiz explores the fundamental concepts of molecular genetics, including gene structure, mutations, and their implications for human health. It also covers the classification of genetic disorders, diagnostic techniques, and Mendelian inheritance. Engage with activities focused on molecular diagnostics and emerging tools in genetics.