Complex inheritance Flashcards
Non-Mendelian patterns of inheritance are
not predictable
Types of non-Mendelian disorders
- de novo mutations
- mosaicism
- mitochondrial inheritance
- trinucleotide repeat disorders
- genomic imprinting disorders
Most diseases are
polygenic
De novo dominant diseases
are sporadic, no family history
caused by a new GERMLINE mutation (in parental gametes)
Inc+ risk with parental age
can be severe, esp. common in developmental disorders
Mosaicism
presence of more than one genetic subtype in genetically related cells - only some cells express the phenotype (can be hard to diagnose because of this)
Two types:
1. Germline mosaicism in unaffected parent
- Somatic mosaicism in child
e. g. mosaic monosomy 7 (one copy=lethal, 2 copies severe developmental delay)
Mitochondrial inheritance
maternal inheritance
genes essential for energy production
severity can be affected if there is heteroplasmy
e.g. MIDD (maternally inherited diabetes and deafness), LHON (leber hereditary optic neuropathy)
Epigenetics
Heritable changes of DNA modification
rather than mutation of the DNA itself
Heritable epigenetic changes can involve (3)
DNA methylation (at cytosine)
Histone modifications
ncRNA
Genomic imprinting (epigenetics)
expression of gene is dependent on the parent of origin (e.g. mum’s is switched off and dad’s is on)
most genes are expressed from both alleles
a few are only expressed when inherited from one parent
methylation status depends on parent of origin
Parent of origin effects
phenotypic effect depends on whether the allele is inherited from the mother or the father
e.g. prader wili, angelman
Prader-wili
deleted paternal 15
obesity, diabetes, mental retardation
Angelman
maternal deleted 15
mental retardation, petite, happy, hand flapping
Multifactorial inheritance
the interaction between genetic and environmental factors
tend to cluster in families but incidence >5%
are ‘on a spectrum’ with genetics at one end and environment at the other
Polygenic inheritance
due to genetic variation
involves many genes with small additive effects
e.g. asthma, diabetes, cancer
Monogenic diseases can be (3)
autosomal dominant, autosomal recessive, or x linked
