Genetics Lectures 5&6

Front 1

Somatic Mosaicism
-&3 examples

Back 1

-post-zygotic mutation which affects certain percentage of cell in an individual

•Examples:
Mosaic Down Syndrome, Segmental Neurofibrosis, McCune-Albright Syndrome

Front 2

Gonadal Mosaicism
-when do you detect it on a
pedigree?

Back 2

-mutation in gonads but not in somatic cells, statistically more likely to be in sperm

-Detected when 2+ children with AD disorder in presence of neg. family history

Front 3

Uniparental Disomy (UPD)
-heterodisomy
-isodisomy

Back 3

-hetero: one of each homolog

-iso: two copies of same chromosome

Front 4

Rescue mechanisms of UPD

Back 4

oTrisomy “rescue”

oFertilization of null gamete by diploid gamete

oCompensatory duplication of monosomy

Front 5

Genomic imprinting & mechanism

Back 5

-different modification of maternal/paternal copies

oMethylation before fertilization, usually associated with gene silencing, is stably transmitted through mitosis/somatic cells, reversed if need be due to gender of child

Front 6

Prader-Willi & Angelman
-&can you diagnose with FISH?

Back 6

•Prader-Willi Syndrome
o Clinical Symptoms:
hypotonia, mental retardation,
obesity
o Caused by deletion of
paternal allele on
chromosome 15 or UPD
-Gene from mom imprinted

•Angelman Syndrome
o Clinical Symptoms: severe
mental retardation, movement
disorder (puppet like),
seizures
o Caused by deletion of
maternal allele on
chromosome 15 or UPD
-Gene from dad imprinted

-FISH assay does NOT mean you know which chromosome has the deletion which would determine which disease the kid has

Front 7

Fragile X Syndrome

Back 7

oClinical Symptoms: Most common inherited form of mental retardation

oDue to unstable CGG repeats, expansion of repeat only occurs through female meiosis
-CpG island methylated in full
mutation

oOnly about half of females express when carry full mutation b/c they have two X chromosomes

Front 8

Myotonic Dystrophy

Back 8

oClinical Symptoms: Myotonia, cataracts, cardiac arrhythmias, endocrinopathies

oUnstable GCT repeat, expansion can occur by either mom or dad
-Congenital (severe) form with
maternal transmission only

Front 9

Huntington Disease

Back 9

oTypically found without anticipation, usually parents have same # of repeats as kids
-Exception: anticipation seen
with juvenile-onset, only
paternal

oClinical Symptoms: Progressive involuntary movements, cognitive loss, depression

oCAG repeats (encodes glutamine)

Front 10

-Polygenic trait
-Multifactorial trait
-Quantitative trait

Back 10

-Polygenic trait: combined influence of multiple genes

-Multifactorial trait: combined influence of multiple genes + environment

-Quantitative trait: additive effects of genetics + environment & can be measured on numerical scale (height, weight, BP)

Front 11

Threshold traits

Back 11

•Trait either present or absent

•Bell-shaped distribution on liability curve & only those exceeding threshold effected
oLiability curve = combination of
genes & environment & more
you have of those higher you
are on liability curve
oDon’t see spinal bifida (neural
tube defects) b/c folic acid
added to diet & can be picked
up by ultrasound (she said hint
hint?)

Front 12

Rules for Multifactorial Inheritance

Back 12

oRecurrence risk is HIGHER if 1+ family member affected

oGreater the severity, HIGHER risk

oRecurrence risk greater if proband of the less commonly affected sex
-Pyloric stenosis example

oRecurrence risk decreases rapidly in remotely related individuals

oRecurrence risk for 1st degree relatives is relatively square root of population incidence