MCBHD Flashcards

Question

About Down's syndrome

Answer 1

``` Trisomy 21 95% patients NDJ (usually maternal meiosis I) 5% robertsonian chromosome ~2% mosaic 'Order egg model' - maternal age effect ```

Answer 2

1 in 650-1000 live births Most common cause of mental retardation Hypotonia, particularly in newborn period Developmental delay Cardiac abnormalities; AV canal defects most common GI abnormalities; duodenal stenosis/atresia, imperforate anus, Hischsprung disease ALL/AML - 10-20 x relative risk Conductive hearing loss Features of Alzheimer's >40 years

Answer 3

``` Trisomy 18 Incidence ~1 in 6000 live births Intrauterine growth retardation Micrognathia Cleft lip +\- palate Short palpebral fissures Fixed flex ion deformities of fingers Heart defect >95% - VSD/ASD/PDA Inguinal/diaphragmatic hernias Renal malformations ```

Answer 4

Trisomy 13 - primary or secondary robertsonian translocation ~1 in 10,000 live births Midline defects: hyotelorism, holoprosencephaly,midline cleft lip/palate, scalp defect Post axial polydactyly Heart defects/renal abnormalities Survival - most die by 1 month

Answer 5

- males are squares - females are circles - partners have a line between them - siblings have a line above them - there is a line down for children - affected people are shaded in - carriers have dots in

Answer 6

- incidence 1/4000 female births - 45X0 or mosaic (45X0/46XX, 45 XO/47XXX, 45X0/46XY) - >60% miscarry - high incidence in spontaneous abortions (9-10%) - raised at nuchal translucency/cystic hygroma - at birth: oedema of hands and feet, neck webbing, coarctation of aorta, renal malformation - short stature - infertility secondary to gonadal dysgenesis - intellectually normal

Answer 7

- 45X/46XY mosaicism - usually normal male (90%), but with potential for gonadoblastoma - mosaicism with ring or isochromosome Xq results in variant Turner syndrome

Answer 8

- 47XXY - incidence 1/1000 male live births - phenotype mild and variable - some cases undetected - Barr body present - NDJ paternal meiosis I (50%), others NDJ maternal meiosis or zygotic mitotic error (mosaic) - variants 48,XXYY, 48,XXXY etc

Answer 9

- may present prenatally, during childhood with behavioural problems, or adulthood with infertility - tall stature - eunuchoid body habitus - some behavioural and minor learning difficulties - lack of secondary sexual characteristics - treat with testosterone - infertility

Answer 10

Approximately 1/400 newborns have a structural rearrangement BALANCED: no net gain or loss of genetic material UNBALANCED: net gain or loss of genetic material RECIPROCAL or ROBERTSONIAN usually no deleterious phenotype unless breakpoint affects regulation of a gene

Answer 11

- two afrocentric chromosomes join near centromere with the loss of p arms - balanced carrier has 45 chromosomes - if 46 chromosomes present including Robertsonian then must be unbalanced - P arms encode rRNA (multiple copies so not deleterious to lose some) - 13q14q and 14q21q relatively common

Answer 12

- breakage and loss of eccentric fragment - terminal or interstitial - monosomic region - haploinsufficiency of some genes - phenotype usually abnormal and specific for size and place of deletion - 1/7000 live births

Answer 13

- many patients has no abnormality visible on metaphase spread - high resolution banding, FISH and now CGH showed 'micro' deletions - only a few genes may be lost or gained - contiguous gene syndrome - areas of low copy number repeat sequences - recombination error?

Answer 14

chromosome analysis pre and post-natal testing, adult testing: foetal blood, amniotic fluid, CVS biopsy, solid tissue; venous blood, tumour tissue WHY?: ambiguous genetalia/indeterminate gender, known familial chromosome rearrangement, multiple miscarriages HOW?: G-banding, FISH, QF-PCR, array-CGH

Answer 15

- giemsa stain - metaphase - line up based on size, banding and centromere position uses a chemical stain, uses metaphase chromosomes, takes several days at least, looks for aneuploidies, translocations and very large deletions

Answer 16

Chromatin: 2 different sorts: euchromatin and heterochromatin, euchromatin = GC-rich; loosely packed; genes active, heterochromatin = AT-rich; tightly packed; genes inactive, stain differently

Answer 17

1. fluorescent probe 2. denature probe and target DNA 3. mix probe and target DNA 4. probe binds to target

Answer 18

- 22q deletion syndrome - prader-willi syndrome (chromosome 15) - cri-du-chat (chromosome 5) You have to know what causes a disease in order to be able to test for it by standard FISH, because you have to be able to design a specific probe.

Answer 19

- quantitative fluorescence PCR - triremes 13, 18 and 21 - uses microsatellites - looks at how many copies of a chromosome the patient has - uses fluorescent probes for specific micro satellite markers on specific chromosomes - uses extracted DNA - quick (~48 hours) - looks for aneuploidies - need to know what you're looking for

Answer 20

di, tri, tetra, penta, hexa nucleotide sequence with a variable number of repeats - number of repeats is constant within an individual - number of repeats varies between individuals

Answer 21

- comparative genomic hybridisation - sub-microscopic chromosome abnormalities (~60kb) - micro deletions, micro duplications, CNVs - main indication = developmental problems, dysmorphia - uses fluorescent probes to differentiate between patient and control - uses extracted DNA - looks for deletions and duplications

Answer 22

- deletions/duplications - 10kb-5000kb - can protect e.g. from HIV - can be detrimental e.g. autism and schizophrenia - many do nothing - ~12% of the genome = CNV

Answer 23

1. extract DNA 2. test DNA labelled with fluorescent dye 3. control DNA labelled with different fluorescent die 4. mix DNA tighter 5. apply denatured DNA to array --> hybridise 6. measure relative fluorescence

Answer 24

- DNA isolation and amplification (generally each exon separately) - denature - anneal primer - extend - terminate - denature - read; sort fragments and determine sequence DNA fragments are drawn through the capillary; the smaller fragments pass through more quickly than larger fragments

Answer 25

- targeted - whole exome - whole genome Looks at each base and identifies small substitutions and small indels. It can look at ALL the genes at once and uses different chemistry from Sanger sequencing.