CMMB 413 chapter 6 Flashcards
Autosomal Chromosomal disorders
-gene dosage
Sex chromosomal disorders
- involved in sex determination
- subject to different forms of genetic regulation
Microdeletions and how to detect large deletion
- small regions deleted rather than big portions
- Large deletion: karyotyping (costs the least), FISH, CGH= MORE EXPENSIVE
- small microdeletions: PCR
Trisomies in which 3 chromosomes and why
21, 18, 13; are the most gene poor
Down Syndrome
1/800 births associated with increased maternal age 100% btw MZ twins 100% discordance btw DZ twins and other family members karyotype 47XX/Y, +21
Down Syndrome Phenotype
-hypotonia: poor development of muscles
-low set ears
-flat nasal bridge
-open mouth, protruding tongue
IQ~30-60
1/3 liveborn infants have congenital heart disease
15X increased risk leukemia
increased risk of heart disease
DS Causes (5)
95% trisomy= chromosome 21 not the entire 21 4% Robertsonian Translocation 21q21q Translocation Mosaic Down Syndrome Partial Trisomy
recurrence risk
6 possible gametes, 3 are viable and of those 1/3 theoretical chance that the progeny are trisomic
mother carrier: 10-15% of progeny trisomic
father carrier: ~3% of progeny trisomic
21q21q Translocation
isochromosome
Testing for DS
biochemical screening; Ultrasound (thickness in neck); amniocentesis; chorionic villus sampling
Mosaic Down Syndrome
- 2% of patients
- wide variability of phenotypes: depends on when mosaic occurs; earlier it happens in the development you see more phenotypes
Partial Trisomy
very rare
duplication of part of 21q
very small!!
Chorionic villus sampling
placenta is embryonic tissue so for this test you have to take cells from it
-can do this 10-12 week period
When to use prenatal diagnosis
if the risk that the child has DS outweighs the risk that the procedure will lead to fetal loss (family history or age factor)
Amniocentesis
sampling the amiotic fluid can use different techniques like CGH to test for the disorder
-can be performed at 14 weeks
Trisomy 18
1/7, 500 births; survival>3 months rare 60% patients females older maternal age can be trisomic, translocation, or mosaic 95% are aborted before they are born
Trisomy 18 Phenotype
mental retradation, failure to thrive severe heart deformations receding jaw hypertonia (extreme muscle tone) clenched fist; fingers 2&5 overlap 3&4 rocker bottom feet
Trisomy 13
- very rare, 1:15-25000
- 1/2 of patients die in 1st month
- maternal age factor
- nondisjunction at M1
- unbalanced translocation
- cleft lip
- polydactyl (extra finger)
segmental aneusomy
deletions that give rise to clinically recognizable syndromes
contiguous gene syndrome
deletion of many continuous genes leading to haploinsufficiency
Autosomal Deletion Syndromes
1/7000 births; cytogenetically visible
deletion regions have many genes
Cri du Chat
deletion of a portion of chromosome 5
1% of all institutionalized mentally retarded patients
Testes Determining Factor
- first signal deciding sex
- SRY gene: encodes a transcription factor
Unusual Recombination of X and Y
X and Y outside of the pseudoautosomal region can result in an XX MALE and an XY FEMALE
SRY gene on an X chromosome= testis formation
XX males are not fertile because they dont have the AZF gene (no sperm production)
X and Y pairing during meiosis
pseudoautosomal regions= only place where they can recombine= only place that is homologous
X chromosome
has many genes that are used in males and females
X inactivation
random inactivation of one X in females
-heterochromatic (Barr Body)
once an X chromosome is inactivated all daughter cells have the same X inactivated
how is the X chromosome inactivated?
by jumbling up into heterochromatin and remain inactive
How are Xi genes inactivated
inactivated by methylation and/ or histone modification
what % escapes inactivation
10%
XIST
- inactive X specific transcript (not completely inactivated some loci still expressed)
- only expressed from inactive X chromosome
- encodes noncoding RNA that doesnt leave the nucleus
Sex chromosome Abnormalities
- most common of all genetic disorders
- less severe phenotypes than similar autosomal aneuploidies
four most common syndromes
a) Klinefelter Syndrome (47,XXY)
b) 47, XYY Syndrome
c) Trisomy X (47, XXX)
d) Turner (45, X)
Klinefelter Syndrome Phenotypes
-tall, thin
-long legs
-hypogonadism
-underdeveloped secondary sexual characteristics
-gynecomastia
-infertile
-low androgen
-one X chromosome inactivated
-gene dosage: higher dosage of genes that arent inactivated
XXY= phenotypically male with feminization ( development of breasts)
47 XYY (When does non-disjunction happened?)
M2
Trisomy X (47, XXX)
not abnormal phenotypically most undiagnosed usually fertile 70% have learning problems more X chromosome= more severe phenotype
Turner Syndrome (45 X)
-short stature
-gonadal dysgenesis
webbed neck
-broad chest, widely spaced nipples
-normal intelligence
-99% of 45,X fetuses abort spontaneously
