Cytogenetics and Common Diseases

Question 1

Chromosome abnormalities = leading known cause of pregnancy loss

• ___% of spontaneous fetal losses in 1st T
• ___% of spontaneous fetal losses in 2nd T

Answer 1

• 50% of spontaneous fetal losses in 1st T
• 20% of spontaneous fetal losses in 1st T
• trisomy = MC genetic cause of spontaneous abortion

Question 2

long arm =

Answer 2

• long arm = q

- short arm = p “petite”

Question 3

Karyotypes are arranged from the ____ chromosome to the ____ chromosome

Answer 3

arranged longest to shortest

Question 4

Acrocentric chromosomes

Answer 4

• have the centromere far toward one end
• the p arm contains little info
• 13-15, 21-22

Question 5

Triploid

Answer 5

• 69 chromosomes
• when 2 sperm fertilize one egg at once
• common at conception, most lost prenatally. 1/10000 births
• lethal: multiple heart and CNS defects
• Tetraploid = 1 egg is fertilized by 3 sperm (92 chromosomes); extremely rare, lethal
• examples of euploid (when a cell has a multiple of 23 Ch)

Question 6

Down Syndrome

Answer 6

• Trisomy 21; MC autosomal trisomy
• mental retardation
• short stature
• hypotonia
• depressed nasal bridge, upslanting palpebral fissures, epicanthal fold
• congenital heart defect (endocardial cushion defect) in approx 40%
• increased risk of acute lymphoblastic leukemia
• Alzheimers in 50-60s (amyloid precursor protein, APP gene on Ch 21)
• reduced fertility
• risk increases with AMA
• if caused by nondisjunction during meiosis, not associated with prior pregnancy loss

Question 7

Edward Syndrome

Answer 7

• Trisomy 18
• inward turning, rocker-bottom feet (prominent heels)
• clenched first w overlapping fingers
• congenital heart defects
• low-set ears, micrognathia (small lower jaw)
• mental retardation
• poor prognosis

Question 8

Patau Syndrome

Answer 8

• Trisomy 13
• polydactyly (extra fingers and toes)
• cleft lip, palate
• microphthalmia, mental retardation
• cardiac and renal defects
• very poor prognosis

Question 9

Klinefelter Syndrome

Answer 9

• 47, XXY (Always male bc Y has testes determining factor)
• testicular atrophy (maybe undescended testicles)
• infertility
• gynecomastia
• female distribution of hair
• low testosterone
• elevated FSH and LH
• high-pitched voice
• no mental retardation

Question 10

Turner Syndrome

Answer 10

• 45, X (50%) or 45, XO
• only monosomy consistent with life
• majority of others are mosaics for 45,X and one other cell lineage (46,XX ; 47,XXX, 46,XY)
• females with 45,X or 46,XY are at an increased risk for gonadal blastoma
• short stature
• edema of wrists and ankles in newborn
• cystic hygroma in utero resulting in excess nuchal skin and webbed neck
• primary amenorrhea (never menstruate)
• coarctation of aorta or other central heart defect in some cases
• infertility
• gonadal dysgenesis

Question 11

Nondisjunction is MC in

Answer 11

• 70% of nondisjunction occurs in meiosis I in females
• MC in oogenesis than spermatogenesis
• MC with AMA (bc a woman’s eggs are formed during fetal development and remain in prophase I until ovulation)
• nondisjunction is the usual case of aneuploidies including Down, Edward, Patau, Turner and Klinefelter

Question 12

Assay for Down Syndrome (can detect 70% of fetuses with Down)

Answer 12

serum levels of:

• alpha-fetoprotein
• chorionic gonadotropin
• unconjugated estriol

Question 13

Reciprocal translocation

Answer 13

• when genetic material is exchanged btw non-homologous chromosomes (i.e. btw Ch 2 and 8)
• happens during gametogenesis
• offspring will carry the reciprocal translocation in ALL their cells = translocation carrier
• Karyotype if btw short arms of Ch 2 and 8 in male: 46XY,t(2p;8p)

Question 14

t(9;22)

Answer 14

chronic myelogenous leukemia (c-abl)

Question 15

t(15;17)

Answer 15

acute myelogenous leukemia (retinoid receptor-alpha)

Question 16

t(14;18)

Answer 16

follicular lymphoma (bcl-2 that inhibits apoptosis)

Question 17

t(8;14)

Answer 17

Burkitt lymphoma (c-myc)

Question 18

t(11;14)

Answer 18

mantle cell lymphoma (cyclin D)

Question 19

Robertsonian Translocation

Answer 19

• responsible for 5% of Down Syndrome cases
• MC than reciprocal translocations
• occur only in acrocentric chromosomes (13-15; 21-22)
• involve the loss of the short arms of 2 of the chromosomes and subsequent fusion of the long arms
• suspect in young mother with previous miscarriages
• adjacent segregation produces unbalanced genetic material and most likely loss of pregnancy. Exception: Downs
• alternate segregation produces a normal haploid gamete (and diploid conception) OR a liveborn who is phenotypically normal translocation carrier

Question 20

Wilms Tumor Sx

Answer 20

W: Wilms Tumor
A: aniridia
G: genital abnormalities
R: mental retardation
- result of micro deletion that includes several contiguous genes

Question 21

Williams Syndrome Sx

Answer 21

• hypercalcemia
• supravalvular aortic stenosis
• mental retardation
• characteristic facies
• result of micro deletion that includes several contiguous genes

Question 22

DiGeorge Syndrome Sx

Answer 22

• congenital absence of thymus and parathyroids
• hypocalcemic tetany
• T-cell immunodeficiency
• characteristic facies (cleft palate)
• heart defects
• result of micro deletion that includes several contiguous genes

Question 23

oncogenes generally encode proteins that

Answer 23

• stimulate the cell cycle
• the abnormal alleles encode proteins that are more active than normal proteins
• gain of function; one hit

Question 24

tumor suppressor genes generally encode proteins that

Answer 24

• inhibit the cell cycle or
• participate in DNA repair processes
• abnormal alleles could either produce no protein product = null alleles
• or encode proteins with significantly reduced activity
• loss of function; 2 hits

Question 25

gene involved in coronary heart disease

Answer 25

• LDL receptor gene (apoB-100 receptor gene)

Question 26

gene involved in hereditary nonpolyposis colorectal cancer (HNPCC); lynch syndrome

Answer 26

• hMLH1, hMLH2 genes encoding mismatch repair genes

Question 27

gene involved in adenomatous polyposis colorectal cancer

Answer 27

• APC gene encoding cell adhesion/nuclear signaling protein

Question 28

gene involved in breast cancer

Answer 28

• p53 encodes a protein that halts the cell cycle for DNA repair
• Familial only: BRCA 1, BRCA 2

Question 29

gene involved in Alzheimer disease

Answer 29

• Familial only: BAPP (beta amyloid precursor protein: 21q21)
• Familial only: Presenilin (improper processing of beta-amyloid precursor protein
• sporadic, late-onset: APOE (epsilon4 allele) encoding a variant of ApoE

Question 30

gene involved in Diabetes

Answer 30

• MODY: high heritability, HNF genes, GLK (glucokinase gene)
• IDDM (Ty1): Moderate heritability w linkage to HLA-D (DR3/4) with HLA-DQ (beta) most likely locus. Other non-MHC loci involved
• NIDDN (Ty2): high heritability, multiple susceptibility loci