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Flashcards in Cytogenetics and Common Diseases Deck (30)
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Chromosome abnormalities = leading known cause of pregnancy loss
- ___% of spontaneous fetal losses in 1st T
- ___% of spontaneous fetal losses in 2nd T

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


long arm =

- long arm = q
- short arm = p "petite"


Karyotypes are arranged from the ____ chromosome to the ____ chromosome

arranged longest to shortest


Acrocentric chromosomes

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



- 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)


Down Syndrome

- 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


Edward Syndrome

- 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


Patau Syndrome

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


Klinefelter Syndrome

- 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


Turner Syndrome

- 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


Nondisjunction is MC in

- 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


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

serum levels of:
- alpha-fetoprotein
- chorionic gonadotropin
- unconjugated estriol


Reciprocal translocation

- 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)



chronic myelogenous leukemia (c-abl)



acute myelogenous leukemia (retinoid receptor-alpha)



follicular lymphoma (bcl-2 that inhibits apoptosis)



Burkitt lymphoma (c-myc)



mantle cell lymphoma (cyclin D)


Robertsonian Translocation

- 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


Wilms Tumor Sx

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


Williams Syndrome Sx

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


DiGeorge Syndrome Sx

- 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


oncogenes generally encode proteins that

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


tumor suppressor genes generally encode proteins that

- 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


gene involved in coronary heart disease

- LDL receptor gene (apoB-100 receptor gene)


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

- hMLH1, hMLH2 genes encoding mismatch repair genes


gene involved in adenomatous polyposis colorectal cancer

- APC gene encoding cell adhesion/nuclear signaling protein


gene involved in breast cancer

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


gene involved in Alzheimer disease

- 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


gene involved in Diabetes

- 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