Chap: 6 the chomosomal and genomic basis of disease

Question 1

two chromosomes inherited from two identical sister chromatids

Answer 1

isodisomy

Question 2

both homologues from both parents are present

Answer 2

heterodisomy

Question 3

Heterodisomy indicates what type or error?

Answer 3

meiosis I error

Question 4

Isodisomy indicates what type of error?

Answer 4

meiosis II error

Question 5

Proximal iUPD (with crossing over) results from what type of error?

Answer 5

meiosis II error

Question 6

Distal iUPD (with crossing over) results from what type of error?

Answer 6

meiosis I error

Question 7

occurs from misalignment of and subsequent recombination between the flanking segmental duplications

Answer 7

non-allelic homologous recombination

Question 8

7q11.23 deletion

Answer 8

Williams syndrome

Question 9

15q11-13 deletion

Answer 9

Prader-Willi/Angelman Syndrome

Question 10

Autism/DD

recurrent microdeletion syndrome

Macrocephaly is common

chiari malformation and cerebellar ectopia most frequent brain abnormalities

vertebral anomalies most common birth defect

Answer 10

16p11.2 deletion

Question 11

17p11.2 deletion

Answer 11

Smith-Magenis Syndrome

Question 12

feeding difficulties- infamts

prolonged napping-infants

upper body squeeze/hug

Answer 12

17q11.2 deletion

Smith-Magenis

Question 13

Smith-Magenis Syndrome can also result from intrageneic pathogenic variants in

Answer 13

RAI1

Question 14

Potlocki-Lupski Syndrome

Answer 14

17p11.2 duplication

Question 15

• preauricular pits and/or tag
• anal atresia,
• iris coloboma
• heart defects
• renal anomalies

Answer 15

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

Question 16

3.5Mb deletion

Y chromosome

Oligozoospermia/Azoospermia/Infertility

Answer 16

AZFc

Question 17

true/False: Most cases of cri du chat are sporatic

Answer 17

True

5p deletion

breakpoints are highly variable

Question 18

inv(9)(p11q12)

Answer 18

considered a normal variant

does not appear to have signifigant risk for miscarriage or unbalanced offspring

Question 19

inv(3)(p25q21)

Answer 19

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

Question 20

absence of paternally derived 15q11-q13

Answer 20

Prader-Willi Syndrome

infancy feeding difficalties

childhood hyperphagia and obesity

hypotonia

cognitive impairment

short stature

dysmorphism

Question 21

hypermethylation of one copy of SNRPN

Answer 21

Prader-Willi syndrome

Question 22

NIPTs noted for trisomy 15

Amniocentesis chromosomal analysis is normal

What condition would you be concerned about?

Answer 22

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)

Question 23

which molecular case of Prader-Willi has the highest recurrance risk?

Answer 23

Imprinting center defects: as high as 50%

deletion and maternal UDP about 1%

parents with balanced translocation: up to 25%

Question 24

Majority of case of Beckwith-Weidmann Syndrome are secondary to what molecular defect

Answer 24

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

Question 25

Maternally inherited mutations in ____ account for about ____% of patients with Angelman Syndrome

Answer 25

UBE3A

10%

Question 26

genetic recombination occuring outside the _______ of the sex chromosome. Result in XX males and XY females

Answer 26

pseudoautosomal regions

Question 27

which of the following chromosomal inbalances may have greater clinical signifigance

imbalances on Xp or imbalances in Xq

Answer 27

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

Question 28

most females with a XY karyotype have a normal ____ gene.

Answer 28

normal

Question 29

The DAX1 gene found on Xp21.3 is a transcription factor that has a ____________ role in gonadal sex development

Answer 29

dosage-sensative

duplications of DAX1 supresses the function of SRY leading to failure of testicular development; leading to ovarian development

Question 30

SOX9 mutations found on chromosome 17 are associated with this skeletal malformation, leading to complete gonadal dysgenesis.

Answer 30

camptomelic dysplasia

46,XY