Chap: 6 the chomosomal and genomic basis of disease Flashcards
two chromosomes inherited from two identical sister chromatids
isodisomy
both homologues from both parents are present
heterodisomy
Heterodisomy indicates what type or error?
meiosis I error
Isodisomy indicates what type of error?
meiosis II error
Proximal iUPD (with crossing over) results from what type of error?
meiosis II error
Distal iUPD (with crossing over) results from what type of error?
meiosis I error
occurs from misalignment of and subsequent recombination between the flanking segmental duplications
non-allelic homologous recombination
7q11.23 deletion
Williams syndrome
15q11-13 deletion
Prader-Willi/Angelman Syndrome
Autism/DD
recurrent microdeletion syndrome
Macrocephaly is common
chiari malformation and cerebellar ectopia most frequent brain abnormalities
vertebral anomalies most common birth defect
16p11.2 deletion
17p11.2 deletion
Smith-Magenis Syndrome
feeding difficulties- infamts
prolonged napping-infants
upper body squeeze/hug
17q11.2 deletion
Smith-Magenis
Smith-Magenis Syndrome can also result from intrageneic pathogenic variants in
RAI1
Potlocki-Lupski Syndrome
17p11.2 duplication
- preauricular pits and/or tag
- anal atresia,
- iris coloboma
- heart defects
- renal anomalies
Cat-eye-Syndrome
CES is usually associated with a supernumerary bisatellited marker chromosome containing material of chromosome 22 (idic(22)(pter→q11.2::q11.2→pter)), which results in partial tetrasomy 22.
22q11.2 duplication
3.5Mb deletion
Y chromosome
Oligozoospermia/Azoospermia/Infertility
AZFc
true/False: Most cases of cri du chat are sporatic
True
5p deletion
breakpoints are highly variable
inv(9)(p11q12)
considered a normal variant
does not appear to have signifigant risk for miscarriage or unbalanced offspring
inv(3)(p25q21)
carriers are normal
offspring with 3q21 duplication and 3p25 deletion = abnormal phenotype
offspring with opposite not viable.
40% eprirical risk of abnormal pregnancy outcome for carriers
absence of paternally derived 15q11-q13
Prader-Willi Syndrome
infancy feeding difficalties
childhood hyperphagia and obesity
hypotonia
cognitive impairment
short stature
dysmorphism
hypermethylation of one copy of SNRPN
Prader-Willi syndrome
NIPTs noted for trisomy 15
Amniocentesis chromosomal analysis is normal
What condition would you be concerned about?
Prader-Willi syndrome
Maternal uniparental disomy via trisomy rescue
Loss of paternal chromosome 15 from conceptus with chromosome 15 trisomy secondary to maternal nondisjunction (meiosis II non-disjunction)
which molecular case of Prader-Willi has the highest recurrance risk?
Imprinting center defects: as high as 50%
deletion and maternal UDP about 1%
parents with balanced translocation: up to 25%
Majority of case of Beckwith-Weidmann Syndrome are secondary to what molecular defect
Loss of maternal methylation of IC 2: 50%
paternal UPD for 11p15: 20%
Gain of methylation in maternal IC 1: 5%
heterozygous maternally inherited variant: CDKN1C: 40% familial cases; 5-10 % in cases with no family history
Maternally inherited mutations in ____ account for about ____% of patients with Angelman Syndrome
UBE3A
10%
genetic recombination occuring outside the _______ of the sex chromosome. Result in XX males and XY females
pseudoautosomal regions
which of the following chromosomal inbalances may have greater clinical signifigance
imbalances on Xp or imbalances in Xq
many more genes “escape” inactivation on distal Xp (as many as 50%) than on Xq (just a few percent)
imbalance for genes on Xp may have greater clinical significance than imbalance for genes on Xq, where the effect is largely mitigated by X inactivation
most females with a XY karyotype have a normal ____ gene.
normal
The DAX1 gene found on Xp21.3 is a transcription factor that has a ____________ role in gonadal sex development
dosage-sensative
duplications of DAX1 supresses the function of SRY leading to failure of testicular development; leading to ovarian development
SOX9 mutations found on chromosome 17 are associated with this skeletal malformation, leading to complete gonadal dysgenesis.
camptomelic dysplasia
46,XY
