Non-traditional Genetics Flashcards
examples of non-traditional inheritance (broad categories)
- mosaicism
- genomic imprinting
- unstable triplet repeat mutations
- mitochondrial inheritance
mosaicism is
- presence of 2 or more genotypes in an individual derived from 1 zygote (ONE genome)
- typically result of mitotic error during development
- can be somatic or germline
chimerism
- distinct from mosaicism
- presence of 2 genomes in one individual
- usually result of fusion of 2 zygotes
congenital hyperpigmentation
- results from somatic mosaicism
- male with mental retardation and swirling pigmentation
- *differs from incontinentia pigmenti
diagnosis of congenital hyperpigmentation
chromosome study of skin cells
key of genomic imprinting
- parent-of-origin difference in gene expression -> expression of chromosomal homologs can be different whether chromosome came from mother or father
- due to epigenetic modification (reversible regulation)
how is imprinting done
•usually methylation or changes in chromatin structure
•most imprints erased and restored each new generation
~200 genes known to be imprinted
mechanisms of imprinting disorders
- uniparental disomy
- microdeletions
- imprinting defects
hypothesized mechanism of uniparental disomy
arises from a trisomy with a loss of the extra chromosome leaving 2 from one parent only
key presentation of prader-willi syndrome
•neonatal hypotonia and cryptorchidism (females may have hypolasia of labia minora)
•hypothalmic dysfunction -> lack of satiety -> obesity
•hypogonadotropic hypogonadism
•growth hormone deficiency -> short stature and diminished muscle
•cognitive and behavioral impairment
~1/15,000 births
cause of prader-willi syndrome
lack of expression of PATERNAL genes at 15q11.13
key findings of prader-willi in infants
- hypotonia
- feeding problems
- cryptorchidism
- may be hypopigmented
key findings of prader-willi in children
- obesity
- oppositional behaviors
- learning problems
- short stature -> rx GH
key findings of prader-willi in adults
- type 2 DM
- obstructive sleep apnea
- hypogonadism -> rx hormone replacement
mechanisms leading to prader-willi syndrome
- paternal deletion on chromosome 15q11.13
- maternal uniparental disomy of chromosome 15
- imprinting defect inactivating paternal chromosome 15q11.13
frequencies of mechanisms causing prader-willi syndrome
- paternal deletion 15q11.13 -> 70%
- maternal UPD chromosome 15 -> 25%
- imprinting defect -> 5%
presentation of angelman syndrome
•severe mental retardation with limited speech •ataxic gait •spontaneously happy affect •seizures ~1/15,000 births
cause of angelman syndrome
lack of brain expression of maternally inherited UBE3A gene at 15q11.13
mechanisms of angelman syndrome
- deletion of UBE3A gene on maternal 15q11.13
- mutation of ^
- paternal uniparental disomy of chromosome 15
- imprinting defect deactivating maternal UBE3A on 15q11.13
frequencies of mechanisms in angelman syndrome
- maternal deletion UBE3A on 15q11.13 -> 70%
- mutation of ^ -> 11%
- paternal UPD chromosome 15 -> 5%
- imprinting defect -> 2%
mitochondria are responsible for
- energy production
- fatty acid oxidation
- urea cycle
- porphyrin synthesis
mitochondrial diseases typically refers to defects involving
aerobic metabolism (electron transport chain)
how many proteins are coded for in mtDNA?
13 polypeptide protein subunits
mitochondrial disease can affect
essentially any tissue with a variety of signs and symptoms
systems most affected by mitochondrial diseases
- neurologic
- muscular
- cardiac
MELAS
- =mitochondrial encephalophathy lactic acidosis
- stroke like episodes
- mitochondrial disease
MERRF
- =myclonic epilespy and ragged red fibers
* mitochondrial disease
NARP
- =neurogenic ataxia and retinitis pigmentosa
* mitochondrial disease
CPEO
- =chronic progressive external ophthalmoplegia
* mitochondrial disease
heteroplasmy
- each mitochondria has multiple copies of mtDNA and can have a mixture of normal and mutant DNA
- also multiple mitochondria per cell, can have mixture of normal and mutant mitochondria
treatment of mitochondrial disorders
- no real effective treatment
- often try cofactors ie coenzyme Q10, thiamine, vitamin E, and carnitine
- diet manipulation not tremendously effective
progression of mitochondrial disorders
often progress steadily with increasing involvement of additional systems
