Patterns of Inheritance and Human Genetic Disease

Comprehensive flashcards covering classical and non-classical inheritance patterns, genetic disease mechanisms, and genomic concepts from human genetics lectures.

Chromosomal Disorders

Genetic disorders caused by an excess or deficiency of whole chromosomes or chromosome segments.

Trisomy 21

A chromosomal disorder characterized by an extra chromosome 21 ($47, XX +21$ or $47, XY +21$).

Turner Syndrome

A chromosomal disorder characterized by monosomy X ($45, XO$).

Klinefelter Syndrome

A chromosomal disorder in males characterized by an extra X chromosome ($47, XXY$).

Single Gene Disorders

Diseases caused by pathogenic mutations in a single gene following Mendelian inheritance patterns.

Multifactorial Inheritance

Traits or disorders caused by a combination of multiple genetic and environmental factors.

Dominant Phenotype

A genetic trait expressed identically in both homozygotes and heterozygotes.

Recessive Phenotype

A genetic trait expressed clinically only in homozygotes or hemizygotes.

Penetrance

The probability that a given genotype expresses its clinical phenotype.

Reduced Penetrance

When some individuals carrying a disease-causing genotype do not express the illness.

Phenocopy

An individual expressing a disease phenotype without carrying the disease-causing genotype.

Variable Expressivity

Variation in the severity of disease manifestations among individuals with the same genetic defect.

Pleiotropy

A phenomenon where a single gene mutation produces distinct symptoms across multiple organ systems.

De Novo Mutation

A spontaneous genetic mutation arising in an individual rather than being inherited.

Anticipation

A genetic condition becoming more severe or appearing earlier in successive generations.

Huntington's Disease

An autosomal dominant neurodegenerative disorder caused by $CAG$ repeat expansions in the $HTT$ gene.

Fragile X Syndrome

An X-linked disorder caused by $CGG$ repeat expansions that expand predominantly during maternal transmission.

Neurofibromatosis Type 1

An autosomal dominant disorder characterized by café au lait spots, Lisch nodules, and neurofibromas, with roughly $50\%$ of cases arising de novo.

Marfan Syndrome

An autosomal dominant connective tissue disorder caused by fibrillin mutations that exhibit pleiotropy across skeletal, ocular, and cardiovascular systems.

Complementation

When parents with the same recessive disorder produce unaffected offspring because mutations are in different genes.

Lyon Hypothesis

The principle that one X chromosome is randomly inactivated in female somatic cells.

Barr Body

The condensed, inactive X chromosome visible in female somatic cells.

Manifesting Heterozygote

A female carrier of an X-linked recessive mutation who expresses clinical symptoms due to skewed X-inactivation.

Pseudoautosomal Region

Homologous sequences at X and Y chromosome tips that allow pairing during meiosis.

Sex-Limited Phenotypes

Autosomal traits expressed clinically in only one sex.

Male-Limited Precocious Puberty

A classic example of a sex-limited phenotype where autosomal dominant mutations cause clinical expression only in males.

Sex-Influenced Phenotypes

Autosomal traits expressed in both sexes, but with differing frequencies or severity.

Hemochromatosis

An autosomal disorder causing iron overload that serves as a sex-influenced phenotype, showing lower severity in females.

Allelic Heterogeneity

When different mutations at the same gene locus cause the disease phenotype.

Locus Heterogeneity

When pathogenic mutations in different genes produce the same disease phenotype.

Epistasis

A gene interaction where one gene modifies or masks the expression of another gene.

Incomplete Dominance

An inheritance pattern where the heterozygous phenotype is intermediate between homozygous phenotypes.

Co-Dominance

An inheritance pattern where both alleles in a heterozygote are simultaneously expressed.

Mitochondrial Inheritance

Matrilineal inheritance of traits exclusively through maternal mitochondrial DNA.

Heteroplasmy

The presence of both wild-type and mutant mitochondrial DNA within a single cell.

Oocyte Spindle Transfer

An experimental mitochondria replacement therapy technique used to prevent maternal transmission of mitochondrial DNA diseases.

Mosaicism

The presence of two or more genetically distinct cell lines derived from a single zygote.

Chimera

An organism with genetically distinct cell lines derived from two separate zygotes.

Genomic Imprinting

An epigenetic phenomenon where gene expression depends on which parent transmitted the allele.

Epigenetic Regulation of Imprinting

Primary molecular mechanisms, specifically DNA methylation and histone modification, that silence specific parental alleles.

Prader-Willi Syndrome

A disorder caused by loss of paternal gene expression on chromosome $15q11\text{-}q13$.

Angelman Syndrome

A disorder caused by loss of maternal gene expression on chromosome $15q11\text{-}q13$.

Uniparental Disomy

A condition where an individual inherits both copies of a chromosome pair from one parent.

Trisomy Rescue

An early embryonic process where a trisomic cell line sheds one chromosome.

Heterodisomy

Uniparental disomy from meiosis I non-disjunction, inheriting two non-identical homologs from one parent.

Isodisomy

Uniparental disomy from meiosis II non-disjunction, inheriting two identical duplicate copies of a chromosome.

Continuous Variation

A category of multifactorial traits where characteristics are quantitative and distributed along a spectrum, with disease representing an extreme end.

Multifactorial Threshold Traits

Disorders where disease manifests only when combined genetic and environmental liability exceeds a threshold.