3 non-mendelian inheritance Flashcards
what is imprinting?
is a differential expression of a gene depending of whi gives the gene the mother or the father
how many genes have been reported to have imprinted expression?
about 31
examples
prader willi
angelman syndrome
what is prader-willi syndrome?
hypogonadism
obesity
mental retardation
hypotonia
1 in 10K
hints that will point towards diagnosis of prader willi
- prenatal
- decreased fetal movement
- abnormal fetal position 40% breech
- Infancy
- low normal birth weight
- hypotonia
- feeding problems
- small penis, undescended testicles
- thick sticky saliva
- narrow forehead
- short stature for genetic background
what is the chromosomal abnormality in prader willi?
- chromosome 15
- its and achrocentric chromosome
- well seen with FISH technique
- its a delition in chromosoma 15
- ALWAYS the deletion comes from the DAD
what is the disease caused by a deletion in chromosome 15 that comes from:
a) father
b) mother
a) from the father Prader Willi
b) from the mother: Angelman syndrome (stiff, jerky gait, absent speech. seizures and excessive laughter - called puppet children)
what is angelman syndrome?
- deletion in chromosome 15
- comes from the MOTHER
- delayed neurodevelopment by 6-12 months
- speech impairment
- ATAXIA
- FREQUENT LAUGHTER
- FREQUEN SMILING
- HAPPY
- HAND FLAPPING
- excessive saliva
- SEIZURES
*
what % of prader willi have deletions?
what do the rest have?
- about 70% have deletions
- 25% maternal uniparental disomy
- 5% methylation defects
- <1% trabslocaiton on ch 15
difference mitosis and meiosis
- Mitosis
- occurs in somatic cells
- results in 2 daughter cells with full chromosomes (diploid 46)
- occurs in somatic cells
- Meiosis
- occurs in gonads
- results in haploid cells
what is uniparental disomy?
when you inherit the TWO copies of a gene from only ONE PARENT
- this is an error in MEIOSIS
- M1: heterodisomy
- M2 ISOdisomy
what is the meaning od disomy?
that a gametic cell is diploid instead of being haploid
- this is due to meiosis error
- can be heterodisomy (half from each parent)
- Isodisomy (both halfs from one parent)
mechanisms of Uniparental disomy?
- trisomy rescue
- monosomy rescue
- gamete complementation
whic is an example of contiguous gene syndrome?
Prader willi syndrome PWS
what does methylation do to genes?
it silences them
what is haploinssuficiency?
its when we make the protein but only half od the normal ammount
for ex these patients have fair hair
what genetic test can you do for PWS or angelman syndrome?
methylation analysis
FISH
or PCR
what would be good test for:
- Deletion syndromes
- UPD - uniparental disomy)
- Imprinting
- Deletion
- FISH
- MLPA (Duchene muscular dystrophy)
- UPD
- SNP analysis
- microsatellite
- MLPA
- Imprinting
- MEthylation analysis - for Prader willi
- Angelman (UBE3A mutaitons)
whaqt is the recurrence risk for
- deletions
- methylation defects
- chromosomal rearrangements
- UBE3A mutations
- deletion 1 in 1000
- methylation defects — 50%
- chromosomal rearrangements —- 50%
- UBE3A ———–50%
what are the diseases associated with very SHORT stature and very TALL stature?
very short = Achondroplasia (FGFR3 mutaiton)
very tall = Acromegaly (GNAS1, SSTR5 mutation)
what is the main classification of genetic diseases?
- chromosomal disorders (before birth)
- single gene (from birth to puberty - peak early childhood)
- polygenic (from birth to puberty - peak early childhood)
- multifactorial (adulthood)
- what type of genetic disorder is clefting?
- what is the frequency
- what types fo clefting are there?
- its multifactorial
- 1 in 700 babies
- types
- cleft lip and palate (1 in 1K)
- 50% of all clefts
- 13% with other birth defects
- more common in Asians less common in AA
- Isolated cleft palate 1 in 2K)
- 30% of all clefts
- more in females
- Isolated lip cleft
- 20% of all clefts
- more in males
- cleft lip and palate (1 in 1K)
what are some characteristics of multifactorial traits?
- most parents are unaffected
- recurrence risk increases with # of affected children in a family
- also increases with severity of disease
- also with consanguinity
- which test is the best to detect Prader will and angelman?
Methylation analysis!! (detects 99% of cases!!!)
FISH detects only 70% PWS and 80% angelman
a couple are referred for genetic counseling after their son is Dx with PWS. What is the most likely molecular mechanism?
DELETION!!
A disorder affects males twice as often as females. Which has the highest risk of being affected?
- son of affected male
- son of affected female
- daughter of affected male
- daughter of affected female
son of affected female!!!
because…
the question is saying that males are more often affected… so choose the SON option
female has higher liability
