Lec 5 princp gen inheritance Flashcards
Lyonization
x-inactivation. which X inactivated is random (one x can handle all duties) calico cat
Mosaicism
which cells from a patient have different genotypes (and karyotypes) problems in early cell division
Ex of mosaicism
Down syndrome (some 46XX some 47XX+21)
Klinefelter (some 46XY some 47XXY)
Turner Syndrome (some 46XX, some 45XO)
Meiosis rounds summary
round one is homolougs seperated (randomly align)
second round separates the chromatids (they have been cross overed)
Meiotic errors
Euploid- normal
polyploid- presence of complete set of extra chromosomes (plants)
Aneuploidy- missing or additional individual chromosomes
Examples of non disjunction
Turner syndrome
klinefelter syndrome
downs syndrome
patau syndrome
edwards syndrome
Turner Syndrome
45 XO
female
short
ovarian hypofunction to failure
puberty problems
infertile
webbed neck
normal intell
Klinefelter syndrome
47 XXY
some with no/limited symptoms
some cog/soc/behav difficulties
hypogonadism
tall
infertility
can be mosaic
more X chrom can increase symptoms
Downs syndrome
47XX+21
most common
icreased risk older age
can be due to translocation
Patau syndrome
47XX+13
severe developmental abnormal
most death within 1 week
Edwards syndrome
47XX+18
abnormal develop
perinatal death within 1 year
genomic imprinting
gene silencing (methylated)
one of the alleles is transcriptionally inactive no mRNA produced
30 genes paternally imprinted
70 genes maternally imprinted
other allele will be expressed
genomic imprinting and germ cells
remain throughout lifespan
in germ cells imprints reset at each generation
so erased and reset during meiosis
Prader-Willi syndrome
chrom 15
Imprinting on chrom 15
deletion of the paternal PWS gene thats active and AS thats inactive
short stature, hypotonia, small hands/feet
obesity, intellectual disability
Angelman syndromes
Imprinting on chom 15 has PWS and AS close oppo activity on each copy
maternal copy deletion active AS gene and inactive PWS
severe intellectual disability, seizures
ataxic gait
uniparental disomy
two chromosomes are inherited from the same parent they will have parent-specific imprinting
pleiotropy
individuals with same genotype have multiple phenotypes
proband (propositus)
first diagnosed person in pedigree
Autosomal Dominant inheritance
unaffected individuals do not transmit trait
expected in every generation
recurrent risk 50%
Ex. postaxial polydactyly
autosomal recessive
recurrent risk for heterozygote parents is 25%
affected mate with normal have normal children
higher occurrence with inbreeding
x-linked recessive
hemizygous males
unaffected male dont transmit trait
female transmit 50% of time
all daughters of affected males are heterozygous
X-linked dominant
rare
males transmit to all females
females half and half to offspring
reduced penetrance
frequency a gene manifests itself is called penetrance
some cases 100% with genotype present phenotype
other cases penetrance is less than 100%
ex. retinoblastoma (90%)
variable expressivity
range of phenotypes that vary between individuals with a specific genotype
ex. neurofibromatosis
locus heterogeneity
single disorder, trait , or pattern caused by mutations in genes at different chromosomal loci
osteogenesis and imperfecta
genotype frequency vs allele frequency
hardy weinberg
find population frequencies P2 (AA)
2pq(Aa)
q2 (aa)
consanguinity and recessive diseases
more likely to produce offspring affected by rare autosomal recessive disorders
mortality rates increase among offspring
mitochondrial DNA more or less mutations
MOre mutations due to close to reactive oxygen species
Leber’s hereditary optic neuropathy (LHON)
degen of ret ganglion cells
acute of subacute loss of central vision
part of mitochondria disorders (usually need a threshold of affected mito in order to be expressed)
Mitochondrial encephalomyopathy, lactic acidosis, and stoke-like episodes (MELAS
high energy tissues
stroke and dementia
lactic acidosis
threshold of mitochondria need to be affected to be symptomatic
Multifactorial inheritance
mixuture of polygenic (combined effects multi genes)
and multifactorial (enviro factors variations in trait)
follow both tend to follow bell-shaped distribution
liability distribution
diseases that dont follow bell curve
threshold of liability
this must be crossed before the disease is expressed
for ex if 5 threshold is 5 genes and only 2 mutated then still normal function
