MCM_Final_DSA6 Flashcards
(23 cards)
1
Q
3 Broad Categories of Human Genetic Disorders
A
-
mendelian (single-gene) disorders:
- results from a mutation in single gene
-
large scale chromosomal disorders:
- results from structural or numerical alteration in chromasomes
-
mutagenic disorders:
- results from complex interactions between various forms of a gene (polymorphisms) and environmental factors
2
Q
Large Scale Chromosomal Abnormalities
A
-
occur during the production of gametes
- severe phenotypic consequences
- examples of mutations:
- total number (aneuploidy) of chromosomes vary (+/- copies)
- deletions of sections of the chromosome
- duplications of the sections of chromosome
- rearrangement (translocations) of sections of the chromosome
3
Q
Aneuploidy
A
- +/- in chromosome number
-
Monosomy: LOSS of a single chromosome in diploid geneome
- ex) Turner Syndrome (X0)
-
Trisomy: GAIN of a single chromosome
- ex) Down Syndrome (3 copies of 21)
4
Q
Nondisjunction
A
- paired homologs FAIL to disjoin during meiosis I or II
- can occur in either spermatogenosis or oogenosis
5
Q
Trisomy 21
A
- aka Downs Syndrome
- trisome 21 accounts for 95% of cases
-
ovum is source for 95% of cases
- increases with maternal age
- most common genetic cause for intellectual disability
- origin of extra chromosome is nondisjunction during Anaphase I or II of meiosis
6
Q
Clincal Features of Down Syndrome
A
- has 12-14 character is that CAN develop
- express 6-8 on average
- features:
- flat facial profile
- oblique palpebral fissures
- epicanthic folds
- palmar crease
- clincodactyl
- co-morbidities include:
- congenital heart disease
- leukemia
- Age 40+ = Alzheimers
7
Q
Trisomy 18
A
- aka Edwards Syndrome
- second most common autosomal trisomy after Downs
- death by age 1
- features:
- hypertonia
- prenatal growth deficiency
- characteristic fist clench
- rocker-bottom feet
- receeding jaw (micrognathia)
- low set ears
8
Q
Trisomy 13
A
- aka Patau Syndrome
- incidence is 1:15 K (3rd place)
- features:
- microcephaly (small head)
- sloping forehead
- fist clench
- rocker bottom feet
- polydactyly (extra fingers)
- bilateral cleft lip & palate
- most pregnancies DO NOT lead to live birth
- 50% DIE IN FIRST MONTH
- 90% in first year
9
Q
Mosaic Down Syndrome
A
- 1% of DS patients are MOSAICS (cell mixture of 46 or 47 chromosomes)
- results from MITOTIC disjunction of chr. 21
- symptoms are milder and depend on proportion of abnormal cells
- MATERNAL AGE = NO EFFECT
- Karyotype: 46, XX/ 47, XX, +21
10
Q
X-Inactivation in Sex Chromosomes
A
- in humans, Y chromosome determines maleness
- dosage compensation: since F have XX, they compensate by inactivating one of the X chrom. (“Lyon Hypothesis”)
- Inactive X becomes HIGHLY CONDENSED = Barr Body
- inactivation is random and occurs early (~day 5.5)
- developing female is mosaic of maternal and paternal Xs (50:50)
11
Q
Sex Chromosome Number Mutations
A
- MORE COMMON than autosomal mutations (1:400)
- typical symptoms:
- delayed puberty
- primary or secondary amenorrhea (no periods)
- infertility
- ambiguous genitalia
12
Q
Klinefelter Syndrome
A
-
two + X, 1+ Y
- = male hypogonadism
- risk factor = maternal age > 40
- 90% of cases is 47, XXY
- mosaics possible
- maternal and paternal nondisjunction at FIRST MEIOTIC divison is equal
- Feaures:
- tall height BUT narrow shoulders & chest
- small testes
- secondary sex characteristics underdeveloped
13
Q
Turner’s Syndrome
A
- female hypogonadism
- most common*** sex chr. abnormality ***in FEMALES
- complete or partial monosomy of the X chr.
- 57% are 45, X (26% mosaic, 14% = X structure abnormaliteies)
14
Q
Trisomy X
A
- nondisjunction of female gamete (XX) + X from Sperm
-
delayed development
- delayed motor milestones
- poor coordination
- serious learning problems
- premature menopause
15
Q
Identification of Barr Bodies
A
- used to identify variations in sex chrome numbers
16
Q
Chromosome STRUCTURE Abnormalities
A
- structural abnormaliteies result from:
- chromosome breakage
- recombination errors
- LESS COMMON than Aneuploidy
- balanced structure: chromosome has the normal complement of chromosome material
- unbalance structure: if there is additional* or *missing material
17
Q
Robertsonian Translocation
A
- 4% of Downs: results from TRANSLOCATION of long arm of Chr. 21 onto another chr. (“Robertsonian Translocation”)
- NO RELATION to maternal age
- high risk within families (“Familial Down Syndrome”) when a parents, especially the mother, is a carrier for the translocation
18
Q
Oogenic Chromosomal Translocations
A
-
philidelphia chromosome: translocation between Chr. 9 and 22
- causing chronic myelogenous LEUKEMIA (CML)
- translocation moves the proto-oncogene ab11 (Tyrosine Kinase) from Chr. 9 to bcr on Chr. 22
- = a BCR-ABL1 chimeric protein
- leads to constant tyrosine kinase activity, cell proliferation, ultimately CELL DEATH
- = a BCR-ABL1 chimeric protein
19
Q
DiGeorge Syndrome
A
- results from in 3 Mb deletion within Chr. 22
- occurs from unequal cross over between misaligned sister chromatids
- features:
- craniofacial anomalies
- intellectual diasability
- immunodeficiency
- heart defects
20
Q
Cri-du-chat
A
- results from deletion of small terminal portion on Chr. 5
- features:
- microcephaly (small head)
- hypertelorism (far apart eyes)
- epicanthal folds (monolid)
- low set ears
- sometimes preauricular tags (ear bumps)
- micrognathia (small lower jaw)
- attributed to haploinsufficiency for a gene
21
Q
Diagnostic Testing During Pregnancy: Amniotic or chorionic villus sampling (CVS)
A
- fetal cells obtained from amniotic fluid or the chorion or the placenta
22
Q
Diagnostic Testing During Pregnancy: Nuchal Translucenecy (NT) Scan
A
- measures the clear (transleucent) space in the tissue on the back of baby’s neck
- 11-14 week ultrasound
23
Q
Diagnostic Testing During Pregnancy: Noninvasive prenatal genetic diagnostic (NIPGD)
A
- fetal cells and DNA obtained from maternal circulation
