NMDP 774 Immunogenetics: Inheritance, Genetic Testing, & Regulation of Gene Expression

General medical genetics concepts including Mendelian patterns of inheritance, genetic testing definitions, population screening principles, and mechanisms of gene expression regulation.

Autosomal Dominant

A pattern of inheritance where disorders are manifested in the heterozygous state ($1$ mutant allele); usually affects every generation and often involves structural proteins or receptors (e.g., Huntington’s disease, Marfan syndrome).

Autosomal Recessive

A pattern of inheritance requiring a homozygous state ($2$ copies of the mutant allele) to manifest; parents are usually carriers and siblings have a $25\%$ recurrence risk (e.g., Tay-sachs disease, cystic fibrosis).

X-linked Dominant

A rare pattern of inheritance where females are more frequently affected; an affected male parent transmits the condition to all of his daughters but none of his sons.

X-linked Recessive

A pattern of inheritance where males are more frequently affected and are described as hemizygous; an affected male transmits the gene to all daughters (making them carriers) but none of his sons.

Mitochondrial Inheritance

Conditions transmitted exclusively through the female to all offspring; both males and females are affected, but males do not pass on the trait.

Hemizygous

A term describing males who have only one copy of X-linked mutant genes on their single X chromosome.

Mitochondrial DNA

The circular chromosome containing $37$ genes found inside mitochondria that encodes specific proteins for mitochondrial function.

Probability of Independent Events

When two events are independent, the probability of both occurring is the product of their individual probabilities ($P(A) \times P(B)$).

Probability of Mutually Exclusive Events

The probability of either of two mutually exclusive events occurring is the sum of their individual probabilities ($P(A) + P(B)$).

Genetic Testing

The analysis of chromosomes, DNA, RNA, proteins, or other analytes to detect abnormalities that can cause a genetic disease.

Genetic Screening

A population-level screening for genetic variants that can cause disease in a person or their descendants, such as newborn screening for inherited metabolic diseases.

Sensitivity

The ability of a screening test to correctly identify affected individuals, calculated as $\frac{a}{a+c}$ (True Positives divided by total affected).

Specificity

The ability of a screening test to correctly identify unaffected individuals, calculated as $\frac{d}{b+d}$ (True Negatives divided by total unaffected).

Positive Predictive Value (PPV)

The probability that a person with a positive screening test result truly has the disease, calculated as $\frac{a}{a+b}$.

Negative Predictive Value (NPV)

The probability that a person with a negative screening test result truly does not have the disease, calculated as $\frac{d}{c+d}$.

Noninvasive prenatal screening (NIPS)

A procedure that evaluates cell-free DNA (cfDNA) from maternal plasma for mutations or aneuploidy without risk of fetal loss.

Incomplete Penetrance

A limitation of genetic testing where a person carries a disease-causing mutation but does not display the symptoms of the disease (e.g., $50\%-80\%$ of women with BRCA1/2 mutations develop breast cancer).

Locus Heterogeneity

A situation where a disease can be caused by mutations in different genes, which may prevent genetic testing from detecting all possible causes.

Gene Expression

The process of generating a protein or RNA product from a particular gene, controlled by mechanisms to conserve energy and only produce proteins when needed.

Epigenetics

Reversible changes in gene expression that do not alter the sequence of the DNA, often involving covalent modifications such as acetylation or methylation.

Invasive Prenatal Diagnosis

Diagnostic testing methods such as Amniocentesis, Chorionic villus sampling, or Percutaneous umbilical blood sampling (PUBS).

Hypophatemic rickets

A disease example of X-linked Dominant inheritance, also known as vitamin D-resistant rickets.

Lesch-Nyhan syndrome

A disease example of X-linked Recessive inheritance.

Leber’s hereditary optic neuropathy

A disease example caused by a mutation in mitochondrial DNA (Mitochondrial Inheritance).