(Lecture 6) Genetic Risk Assessment for Single Gene Disorders

Flashcards defining key terminology, principles of Mendelian genetics, probability laws, Hardy-Weinberg equilibrium, and single-gene disorder risk assessment.

Mendelian Inheritance

An inheritance pattern in which the inheritance of a single mutant allele results in a specific phenotype.

Principle of Segregation

Mendel's law stating that sexually reproducing organisms possess gene pairs that segregate during gamete formation, so that only one copy of each gene pair is transmitted to each gamete.

Principle of Independent Assortment

Mendel's law stating that genes at different loci on separate chromosomes are transmitted independently of one another into gametes.

Alleles

Alternate forms of a gene located at the same locus on autosomal chromosomes.

Homozygous

Having two identical alleles at a specific gene locus (e.g., $AA$ for homozygous dominant or $aa$ for homozygous recessive).

Heterozygous

Having two different alleles at a specific gene locus (e.g., $Aa$).

Dihybrid Cross

A genetic cross between two individuals who are both heterozygous for two distinct gene loci (e.g., $AaDd \times AaDd$), producing a characteristic $9:3:3:1$ phenotypic ratio.

Phenotype

The physically or clinically observed characteristics of an individual, produced by the interaction of genotype with the genetic and external environment.

Genotype

The specific genetic makeup or allele combination present at a given gene locus in an organism.

Multiplication Rule (AND Rule)

A probability rule stating that if two trials or events are independent, the probability of obtaining both specified outcomes is the product of their individual probabilities (e.g., $\frac{1}{2} \times \frac{1}{2} = \frac{1}{4}$).

Addition Rule (OR Rule)

A probability rule stating that the probability of obtaining either one outcome or another mutually exclusive outcome is calculated by adding their individual probabilities together (e.g., $\frac{1}{4} + \frac{1}{4} = \frac{1}{2}$).

Hardy-Weinberg Principle

A mathematical model used to calculate gene and genotype frequencies in a population using the equilibrium equations $p + q = 1$ and $p^2 + 2pq + q^2 = 1$.

Panmixia

Random mating within a population with respect to the specific genotype or trait of interest.

Requirements for Hardy-Weinberg Equilibrium

Four population conditions consisting of: large population size, no natural selection for or against any genotype, random mating (panmixia), and a negligible rate of new mutations.

Sickle Cell Disease Carrier Frequency in African Americans

The calculated carrier frequency ($2pq$) of approximately $0.08$ (~$1$ in every $12$ African Americans), based on an autosomal recessive disease prevalence ($q^2$) of $1/600$ births.

Cystic Fibrosis Carrier Frequency in Europeans

The calculated carrier frequency ($2pq$) of approximately $0.04$ (~$1$ in every $25$ Europeans), based on an autosomal recessive disease prevalence ($q^2$) of $1/2500$ births.

CFTR Gene

A gene encoding an ATP-binding cassette (ABC) transporter that functions as a cyclic AMP (cAMP)-regulated chloride ion channel ($Cl^-$); mutations in this gene cause cystic fibrosis.

Class I CFTR Mutation

A protein production mutation class in cystic fibrosis where no functional CFTR protein is created, typically due to nonsense, splice, or deletion mutations (e.g., G542X, W1282X, R553X).

Class II CFTR Mutation

A protein processing mutation class where CFTR protein is created but misfolds, preventing it from reaching the cell surface (e.g., F508del, N1303K, I507del).

Class III CFTR Mutation

A gating mutation class in which CFTR protein reaches the cell surface, but the channel gate does not open properly (e.g., G551D, S549N).

Class IV CFTR Mutation

A conduction mutation class in which CFTR protein reaches the cell surface, but channel function and ion conductance are faulty (e.g., D1152H, R347P, R117H).

Class V CFTR Mutation

An insufficient protein mutation class in which normal CFTR protein reaches the cell surface, but in insufficient quantities (e.g., 3849+10kbC->T, 2789+5G->A, A455E).