non-mendelian Flashcards
exam 1
any pattern of inheritance in which traits do not segregate in accordance with Mendel’s laws
non-mendelian inheritance
examples of non-mendelian inheritance
- mitochondrial
- trinucleotide repeats
- mosaicism
- Genomic imprinting
- multifactorial
- chromosomal
maternal inheritance
mitochondria. only mitochondria from oocyte contribute to zygote
MELAS
Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes
common features of MELAS
hearing loss, diabetes, seizures, intellectual disability, cardiomyopathy
mixture of normal and abnormal mtDNA
heteroplasmy
all mtDNA is the same
Homoplasmy
a certain percentage of abnormal mtDNA is tolerated without symptoms
threshold effect
how can the percentage of abnormal mtDNA can change over time
random genetic drift, and selective advantage
____ function decreases with age
mitochondrial
tissues with high energy requirements are most likely to be affected (brain, muscle…)
mitochondrial diseases
usually are stable during mitosis and meiosis and are present throughout the genome
trinucleotide repeats
sequence copy number is transmitted as ____________ from parent to child in trinucleotide repeat disorders
polymorphism
increasing severity or earlier onset of a phenotype in successive generations
anticipation
_______ relationship between repeat copy number and severity of phenotype
direct
example of anticipation
myotonic dystrophy, fragile x syndrome, Huntington’s
myotonic dystrophy
affects skeletal and smooth muscle as well as the eye, heart, endocrine system, and CNS
sustained muscle contraction
myotonia
spectrum of severity (5)
normal premutation mild classic congenital
most common inherited cause of intellectual disability
fragile x syndrome
caused by CGG repeat expansion in FMR1 gene on X chromosome
fragile X syndrome
the severity of intellectual disability does or does not increase with repeat size (Fragile X)
does not
female carriers in fragile x have increased risk of
premature ovarian insufficiency
males who have fragile x are at risk for
associated tremors and ataxia syndrome (fxtas)
Presence of more than one cell line in an individual
mosaicim
two types of mosaicism
gonadal
somatic
usually caused by a post-zygotic mutation and can cause a variable degree of disease severity
somatic mosaicism
may be less severely affected than individuals with full trisomy 21
mosaic down syndrome
True or False:
some disorders are only seen in mosaic form because the non-mosaic form is lethal
true
example of a lethal form of mosaicism
pallister-killian syndrome
mosaic tetrasomy 12p
pallister-killian syndrome
pallister-killian syndrome characteristics
low muscle tone, characteristic facies, high arched palate, hypopigmentation, supernumerary nipples, developmental delays, diaphragmatic hernias
_____ mosaicism individual unaffected with the condition
gonadal
mutation occurred in precursor egg or sperm cell
gonadal mosaicism
why is gonadal mosaicism important for recurrence risk assessment?
for apparently de novo dominant disorders
inferred when at least two offspring have an autosomal dominant disorder with no other family history
Gonadal mosaicism
true or false:
you can test for individual sperm/eggs for gonadal mosaicism
false
the difference epigenetic modification on the maternal and paternal genetic contributions to the zygote
imprinting
genomic imprinting mechanisms
uniparental disomy
heterozygous deletion
mutation
methylation of the gene results in
no protein
imprinting reset before
oogenesis or spermatogenesis
_____ is evidence for imprinting
triploidy
the presence of three sets of chromosomes instead of the usual two
triploidy
two sets of maternal chromosomes and one set of paternal chromosomes
digynic triploidy
two sets of paternal chromosomes and one set of maternal chromosomes
diandric triploidy
ver small fetus and placenta
digynic triploidy
normal to small fetus with a large cystic placenta
diandric triploidy
evidence of uniparental disomy
cystic fibrosis
possible explanations of uniparental disomy
non-paternity
de novo mutation
large deletion on paternal chromosome
maternal uniparental disomy
growth disorder with prenatal onset
russell silver syndrome
examples of uniparental disomy and imprinting
russell silver
true or false: not all uniparental disomy results in a phenotype
true
paternal UPD
6, 11, 14, 15
maternal UPD
7, 14, 15, 16
caused by lack of expression from genes in the critical region that are normally expressed from the paternal allele
Prader- Willi syndrome
Prader-willi
pathological overeating (hyperhagia), hypotonia, intellectual disability
caused by lack of expression from genes in the critical region that are normally only expressed from the the maternal allele
Angelman
Angelman syndrome
severe intellectual disability, movement disorder, seizures
Hypotheses as for why does mitochondrial function decrease with age?
- Damage to mtDNA from free radicals due to ox phos
* Increased mutation rate due to lack of repair
