Multifactorial Inheritance and Genomic Imprinting - Vocabulary Flashcards

Vocabulary flashcards covering key terms and definitions from the notes on multifactorial inheritance and genomic imprinting.

Multifactorial inheritance

Trait influenced by multiple genes (polygenic) plus environmental factors; often threshold-based in expression (examples: type 2 diabetes, cleft lip/palate).

Polygenic inheritance

Trait controlled by many genes (usually >10), each with a small additive effect; results in continuous variation (e.g., height, skin color).

Oligogenic inheritance

Trait influenced by a small number of genes (2–5) with moderate effects; can cause variable disease severity (e.g., some epilepsy, congenital heart disease).

Monogenic disease

Disease caused by mutation in a single gene with a typically clear Mendelian pattern.

Threshold model

In multifactorial diseases, there is an underlying liability distribution and disease appears when liability crosses a threshold.

Liability

Cumulative genetic and environmental predisposition to a disease; not directly observable. besitzen a normal distribution in a population.

Recurrence risk (multifactorial)

Probability that a disease recurs in a family; higher if more relatives are affected, if the proband is more severely affected or of the less commonly affected sex, and often decreases with more distant relatives.

Concordant

In twin studies, both individuals in a pair have the same trait.

Discordant

In twin studies, only one individual in a pair has the trait.

Genome-wide association studies (GWAS)

Studies that scan the entire genome to identify susceptibility loci associated with diseases.

Heritability

Statistical measure of the proportion of variation in a trait within a population due to genetic differences.

Epigenetics

Heritable changes in gene expression that do not involve changes to the DNA sequence (e.g., methylation, acetylation, chromatin changes).

Genomic imprinting

Epigenetic phenomenon where gene expression depends on the parent of origin; marks are established in germ cells and maintained through cell divisions.

Imprinting

Process by which an allele is silenced depending on whether it is inherited from the mother or father (often via methylation or other epigenetic marks).

Prader-Willi syndrome (PWS)

Imprinting disorder at 15q11-13 due to loss of paternal gene expression (paternal deletion or maternal UPD); features include neonatal hypotonia, obesity, hypogonadism, and intellectual disability.

Angelman syndrome (AS)

Imprinting disorder at 15q11-13 due to loss of maternal UBE3A expression (maternal deletion, paternal UPD, or UBE3A mutation); features severe developmental delay, seizures, ataxia, and a happy demeanor.

Beckwith-Wiedemann syndrome (BWS)

Imprinting disorder at 11p15 with dysregulation of IGF2/H19/CDKN1C; often due to paternal UPD or loss of maternal imprinting; presents with overgrowth, macroglossia, organomegaly and tumor risk.

Silver-Russell syndrome (SRS)

Imprinting disorder at 11p15 (IGF2/H19) or maternal UPD of chromosome 7; growth restriction, triangular face, feeding difficulties.

Transient Neonatal Diabetes Mellitus (TNDM)

Diabetes present in the neonatal period due to paternal UPD or abnormal methylation at 6q24; typically resolves by about 18 months.

Kagami-Ogata syndrome

Imprinting disorder at 14q32 (DLK1, MEG3) with paternal UPD or maternal imprinting defect; features include polyhydramnios, small thorax, and abdominal wall defects.

Temple syndrome

Imprinting disorder at 14q32 (DLK1, MEG3) with maternal UPD or paternal imprinting defect; features growth retardation, hypotonia, and precocious puberty.

Paternal UPD

Uniparental disomy where both copies of a chromosome or chromosomal region are inherited from the father; can disrupt imprinting.

Maternal UPD

Uniparental disomy where both copies of a chromosome or chromosomal region are inherited from the mother; can disrupt imprinting.

IGF2

Imprinted gene at 11p15; typically paternally expressed; promotes growth; dysregulation contributes to imprinting disorders (e.g., BWS, SRS).

H19

Imprinted gene at 11p15; maternally expressed; non-coding RNA that is typically opposite to IGF2 expression; involved in imprinting regulation.

DLK1

Imprinted gene at 14q32 involved in growth and development; part of the Temple/Kagami-Ogata imprinting region.

MEG3

Imprinted gene at 14q32; non-coding RNA involved in imprinting regulation with DLK1.

FTO

Fat mass and obesity-associated gene; common variants are linked to increased BMI and obesity risk.

MC4R

Melanocortin 4 receptor; key regulator of appetite; variants associated with obesity and altered energy balance.

LEP

Leptin gene; encodes leptin; variants can cause obesity due to disrupted appetite signaling.

LEPR

Leptin receptor gene; variants can lead to obesity from impaired leptin signaling.

POMC

Proopiomelanocortin gene; precursor to several peptides including ACTH; mutations can cause obesity and endocrine issues.

BDNF

Brain-derived neurotrophic factor; influences energy balance and eating behavior; variants linked to obesity risk.

PCSK1

Proprotein convertase subtilisin/kexin type 1; involved in processing POMC; variants associated with obesity.

SNP

Single-nucleotide polymorphism; a common genetic variation that may contribute to disease risk.

APOE ε4

A variant of the apolipoprotein E gene associated with increased risk of Alzheimer’s disease.