Cytogenetics Iii

Front 1

What do leydig and sertoli cells secrete?

Back 1

Leydig--testosterone
Sertoli--mullerian-inhibiting hormone

Front 2

Testosterone causes what to form?

Back 2

Wolffian ducts, penis, scrotum

Front 3

What part of the y chromosome confers maleness?

Back 3

Distal Yp

Front 4

3 functions of sry

Back 4

1. Differentiation of sertoli cells
2. Induces migration of cells from mesonephros into gen ital ridges
3. Induces proliferation of cells in genital ridges

Front 5

Percent of genes on X that escape X inactivation

Back 5

15%

Front 6

Percent of genes on X that escape X inactivation in some, not others

Back 6

10%

Front 7

When in life does x inactivation occur?

Back 7

4.5-16 day embryo

Front 8

What stain shows whwn a chromosome replicates?

Back 8

BrdU

Front 9

Name the 5 stages of X-inactivation

Back 9

1. Counting (X:autosoma ratio)
2. Choice
3. Initiation (at Xic locus)
4. Spreading (to entire X)
5. Maintenance (of all clones)

Front 10

What is the gene product ofXist, and what does it do?

Back 10

15 kb untranslate RNA, coats the inactive X chromosome

Front 11

About how many X chromosome genes have been found to escape X inactivation and where are they located?

Back 11

40-50 genes
About 30% of Xp genes escape inactivation but only 3% of Xq genes

Front 12

Name 3 consequences of X inactivation

Back 12

1. Dosage compensation
2. Functional Mosaicism
3. Variability of Clinical Phenotype

Front 13

Name 3 reasons why X inactvation might not be random

Back 13

1. When a gene on one of the Xs is required for normal cell growth/viability
2. Balanced translocation btwn X and autosome (the translocated X uis usually active)
3. Defective x-inactivation process

Front 14

Clinical findings of Turner syndrome

Back 14

nuchal folds
low posterior hairline
edema
pigmented nevi
decreased birth weight
CHD (coarctation of aorta)
short stature
delayed/absent menarche
thyroiditis
delayed secondary sex traits

Front 15

Turner syndrome patients present with what neonatal findings?

Back 15

edema, heart defect, excess nuchal skin

Front 16

The Turner phenotype is most likely due to what?

Back 16

Missing genes on Xp, where genes from both Xs are typicaly expressed

Front 17

Patients with Turner syndrome due to isochromosome Xq are at increased risk for what (unlike regular Turner)

Back 17

autoimmune disease, especially thyroid and irritable bowel disease

Front 18

What percent of patients with Turner syndrome have iXq?

Back 18

Isochromosome Xq=18% of patients with Turner

Front 19

Features of 47, XXX

Back 19

most are pysically normal, slight increase in minor anomalies--tall stature, slight chance of ovarian dysfunction, some MR

Front 20

How do most cases of 47, XXX happen?

Back 20

nondisjunction in maternal meiosis I (age-related)

Front 21

Features of 48, XXXX

Back 21

mild to mederate MR
tall stature
micrognathia
midface hypoplasia
reduced fertility
gonadal dysgenesis

Front 22

Features of 49, XXXXX

Back 22

moderate MR
microcephaly
short stature
upslanting eyes
heart and kidney anomalies
all Xs from mom

Front 23

How do supernumerary sex chromosomes happen (48, XXXX and 49, XXXXX or with a single Y added in)

Back 23

Successive maternal NDJ in both meiosis I and meiosis II--errors in MI increase lieklihod for errors in MII

Front 24

Incidence of male liveborns with Klinefeler syndrome

Back 24

1/1000

Front 25

Features of Klinefelter syndrome

Back 25

hypogonadism
hypogenitalism
gynecomastia
differencesin body hair, muscle mass, fat distribution
variable IQ (depends on mode of diagnosis)

Front 26

What percent of patients with Klinefelter are mosiacs? (47, XXY/46, XY)

Back 26

15%

Front 27

How does Klinefelter usually happen?

Back 27

maternal or paternal NDJ during meiosis

Front 28

Freq. of 47, XYY

Back 28

1/ 1000

Front 29

Name 3 ways that you could get sex reversal due to recombination errors

Back 29

1. During male meiosis, SRY gets transferred to X, get XX male
2. During male meiosis, SRY gets transferred to X, get XY female
3. SRY inhibitor on X could be duplicated, get XY female

Front 30

80% of XX males occur by what mechanism?

Back 30

SRY gene is translocated onto another chromosome (an acrocentric, usually 15)

Front 31

If SRY gets displaced to another chromosome, which 2 are most common? Which is MOST common?

Back 31

15 or X--usually X

Front 32

Campomelic dysplasia is associated with what gene? Where?

Back 32

SOX9, 17q23

Front 33

How should you manage a newborn with ambiguous genitalia?

Back 33

Don't declare sex immediately
Do chromosomes, FISH for SRY and Y
counsel parents
Rule out CAH
Involves many specialists

Front 34

Features of 1p36 deletion syndrome

Back 34

microbrachycephaly
MR
deep-set eyes
midface hypoplasia
abnormal ears
hearing loss
vision problems
heart defects

Front 35

Thrombocytopenia-absent radius syndrome (TAR) is associated with a deletion of what chromosome?

Back 35

1q

Front 36

Features of 2q37 deletion syndrome

Back 36

intellectual disability
autism
short stature obesity
facial dysmorphism

Front 37

What causes fascioscapulohumeral muscular dystrophy?

Back 37

A deletion of genetic material from D4Z4 at 4q35. The D4Z4 region normally consists of 11 to more than 100 repeated DNA segments, each of which is about 3,300 DNA base pairs (3.3 kb) long. However, in people with facioscapulohumeral muscular dystrophy the D4Z4 region on one copy of chromosome 4 is abnormally short, containing between 1 and 10 repeats.

Front 38

Increased risk of developing Crohn's disease/IBD are associated with changes in areas of which chromosome?

Back 38

chromosomes 5 and 10

Front 39

Deletions of which chromosome can be associated with bladder cancer?

Back 39

9

Front 40

Features of Potocki-Shaffer

Back 40

The characteristic features of Potocki-Shaffer syndrome include openings in the two bones that form the top and sides of the skull (enlarged parietal foramina), multiple benign bone tumors called exostoses, intellectual disability, delayed development, a distinctive facial appearance, and problems with vision.

Front 41

What condition is assoc. with deletion of part of 11p?

Back 41

Potocki-Shaffer

Front 42

Burkitt lymphoma can be caused by a translocation btwn what chromosomes?

Back 42

8 and 14

Front 43

Sensorineural deafness and male infertility is caused by a deletion of what?

Back 43

part of 15q

Front 44

epilepsy, behavioral problems, and autism have all be found to be associated with isodicentric versions of what chromosome?

Back 44

15

Front 45

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is assoc. with which chromosome?

Back 45

16
FOXF1 gene

Front 46

Features of 16p11.2 deletion syndrome

Back 46

delayed development, intellectual disability, and developmental disorders that affect communication and social interaction (autism spectrum disorders)

Front 47

Gene and chromosome assoc. with Rubenstein-Taybi

Back 47

CREBBP, or deletion of 16p13.3

Front 48

What happens with monosomy 7?

Back 48

cancer

Front 49

Benefits of cytogenetics for cancer

Back 49

1. can be predictive of outcome
2. targeted therapies
3. for following minimal residual disease

Front 50

6 steps of prophase of meiosis I, and what happens in each

Back 50

Leptotene-condensation
Zygotenehomologs pair
Pachytene-crossing over
Diplotene-homologs separate
Dictyotene-female cells arrest
Diakinesis-chiasmata resolve

Front 51

Male recombination occurs mostly where?

Back 51

near centromeres

Front 52

Interpret:
46,XX,ins(3)(p21q27q32)

Back 52

The long arm segment between bands 3q27 and 3q32 has broken away and has inserted into the short arm of the same chromosome at band 3p21. The orientation relative to centromere hasn;t changed. Recipient locus listed first.

Front 53

Interpret:
4XY,ins(4;9)(q31;q12q13)

Back 53

q12-q13 of chromosome 9 has inserted into 4q31.Recipient listed first.

Front 54

What is the prognosis for a karyotype missing one copy of 17q?

Back 54

Very bad-missing a p53 gene=cancer