Genetic Disorders (Part 2)

Practice flashcards covering Single Gene Disorders (classical and non-classical) and Complex Multigenic Disorders.

What are the three major groups into which genetic disorders are divided?

Chromosomal disorders, single gene disorders (SGD), and complex multigenic disorders (CMD).

What is pleiotropism in single gene disorders?

A situation where a single gene defect produces multiple different phenotypic effects, such as in sickle cell anemia which can present with hemolysis, kidney infarcts, and bone crises.

What is genetic heterogeneity?

A phenomenon where defects in different genes cause a similar clinical condition, such as defects in about $20$ different genes being implicated in Type 1 DM.

How do dominant and recessive single gene disorders differ regarding allele expression?

Dominant disorders manifest phenotypically in a heterozygous state (one defective allele), whereas recessive disorders manifest in a homozygous state (both alleles of the gene pair are damaged).

What is co-dominance in genetics?

A condition in which both alleles of a gene pair are fully expressed in the phenotype, such as in blood groups and the Major histocompatibility complex.

What is genetic penetrance?

The percentage of individuals carrying a genetic defect who actually manifest the disease phenotypically (e.g., $50\%$ penetrance means $50\%$ of individuals with the defect show symptoms).

What is variable expressivity in single gene disorders?

The occurrence where a single gene defect is expressed in different ways or severities among individuals, such as Type 1 neurofibromatosis ranging from café-au-lait spots to skin tumours.

Why are there no Y-linked classical single gene disorders documented?

Males with mutations affecting the Y-chromosome are usually infertile.

What are the main characteristics of autosomal dominant disorders?

They manifest in a heterozygous state, affect males and females equally, give each child a $50\%$ chance of inheritance from an affected parent, often present in adulthood, and primarily affect structural proteins and receptors.

What are the key characteristics of autosomal recessive disorders?

They manifest in a homozygous state, both parents carry the trait, siblings have a $25\%$ chance of disease, onset is usually early in childhood, penetrance is complete, and they mainly affect enzymes and hemoglobin.

How are X-linked recessive disorders transmitted?

Affected males are hemizygous and manifest the disease; they pass the mutated gene to all daughters (who become carriers) but no sons. Carrier females have a $50\%$ chance of transmitting to sons.

What is the Lyonisation theory?

A theory stating that whenever two or more X-chromosomes are present, only one remains active while the others are inactivated (and usually the mutated X-chromosome is the one inactivated).

What is the inheritance pattern of X-linked dominant disorders?

Affected heterozygous females transmit the disorder to $50\%$ of their sons and $50\%$ of their daughters, whereas affected males transmit the disorder to $100\%$ of their daughters and $0\%$ of their sons.

According to Figure 5.5, what components are involved in this metabolic pathway and its alternate pathway?

The primary pathway converts Substrate to Intermediate 1 (via Enzyme 1), then Intermediate 2 (via Enzyme 2), to Product (via Enzyme 3). An alternate pathway converts Intermediate 2 into M1 and M2. Product also exerts feedback inhibition on Enzyme 1.

What three main consequences can result from enzyme defects in metabolic pathways?

1) Accumulation of substrate, intermediates, or alternate pathway products; 2) Decrease in end products (e.g., albinism due to tyrosinase deficiency); 3) Loss of feedback inhibition leading to overproduction of intermediates.

What are four types of non-classical single gene disorders?

Triple nucleotide repeat mutations, mitochondrial DNA disorders, genomic imprinting associated single gene disorders, and gonadal mosaicism associated disorders.

What is genomic imprinting and how does it occur?

An epigenetic process causing decreased gene expression through DNA methylation and deacetylation in promoter regions, occurring in the ovum or sperm before fertilization and passed to somatic cells via mitosis.

What defines complex multigenic disorders?

Genetic disorders caused by interactions between multiple genes (polygenic) and environmental factors (such as diet, smoking, alcohol, and pollution), characterized by familial clustering after excluding Mendelian and chromosomal inheritance.