Non-Mendelian Inheritance Flashcards
3 Laws of Mendelian Ineritance
- law of dominannce
- law of segregation
- law of independent assortment
3 kinds of mendelian inheritance
automosal dominant, automosal recessive, X-linked
What is non-mendelian inheritance
the inheritance of traits that have a more complex genetic basis than one gene with two alleles and complete dominance - several variants of several genes acting together
Mechanisms of non-mendelian inheritance (give inheritance pattern and associated mechanism)
Learn as LO
- Incomplete Penetrance - environmental factor, genetic modifiers
- Genomic imprinting - variants from parents
- Extranuclear inheritance - e.g. mitochondria mutations
- Anticipation - e.g. triplet repeat expansion
- Complex - multi-genic risk
Compare the environmental and genetic factors which contribute to human diseases
Environmental:
* Common
* Complex genetics
* Multi-factorial
* Low recurrence rate
Genetic:
* Rare
* Genetics simple
* Uni-factorial
* High recurrence rate
what is penetrance
LO
The frequency with which a trait (/mutation) is manifested by individuals carrying the gene
give examples of penetrance
probs don’t learn, just for understanding
CFTR - cystic fibrosis - 100%
BRCA1/2 - Breast cancer - 70-80%
is mutation that causes cystic fibrosis (CFTR) autosomal recessive, dominant or X-linked
autosomal recessive
what else can impact on cystic fibrosis as the CFTR mutation alone does not explain the severity of CF in organs and variation within families
- Genetic modifiers: genes that have small quantitative effects on the level of expression of another gene, may involve polymorphism
- Environmental factors: lifestyle, diet, infection, chemicals…
what is genomic imprinting
- genes expressed from only 1 chromosome
- Parent-of-origin dependent
epigenetic modifications
heritable changes in gene function not explained by changes in DNA sequences - DNA methylation?
Give some genetic mechanisms of imprinting disorders
- Deletions
- Point mutations
- Imprinting errors
- Uniparental disomy (inheritance of chromosome pair from one parent)
Uniparental disomy
occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells or may happen in early fetal development
uniparental diploidy - gyogenic
- 2 maternal genomes
- mass of embryo
- ovarian teratoma
uniparental diploidy - androgenic
- 2 paternal genomes
- mass of placenta
- hydatidiform mole
give 2 examples of imprinting disorders
- Angelman syndrome (epilepsy, mental retardation, inappropriate laughter)
- Prader-Willi Syndrome (PWS) (hypotonia, mental retardation, short stature, obesity)
where is mitochondrial inheritance from
the mother
what is a mutation hotspot
Mitochondria: lacks efficient DNA repair system and protective proteins (e.g. histones) - damaged by reactive oxygen species (e.g. free radicals)
homoplasmy
cell whose copies of mitochondrial DNA are all identical
heteroplasmy
presence of more than one type of organellar genome (e.g. mitochondrial DNA) within a cell
where is disease more common in homoplasmy or heteroplasmy
heteroplasmy - high % mutation
what does mitochondrial disease affect
tissues with high metabolic demand
what is anticpation
A phenomenon in which the signs and symptoms of some genetic conditions tend to become more severe and/or appear at an earlier age as the disorder is passed from one generation to the next
explain multigenic/complex inheritance
where seen, penetrance, what factor is significant to causing it
- often seen in common conditions (e.g. heart disease, breast cancer, autism)
- Multiple low penetrance variants - often extra-genetic affecting expression rather than DNA code
- Rare high penetrance variants in many genes causing same phenotype - schizophrenia
- Environmental factors often significant
role of the environment in genetic disease
Environmental factors such as diet, temperature, oxygen levels, humidity, light cycles, and the presence of mutagens can all impact which genes are expressed, which ultimately affects phenotype
