L8 - Chromosomal deletion and duplication syndromes Flashcards Preview

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Flashcards in L8 - Chromosomal deletion and duplication syndromes Deck (30):

describe deletion and duplication

alteration in chr seq not detectable by karyotype
arise aar of non allelic homologous recombination errors
considered copy no chnages


what more tolerated dup or del



where are dup/del most likely to arise

where repeat seq are similar on the same chr or low copy no
low copy no with 97% seq id also predispose


how do del/dup occur in recomb

misalinment occurs at area where similar or low copy no
unequal crossingover
results in gain or loss of copy no


what are recurrent rearrangements

share breakpoints and common size


what are the nonrecurrent rearrangements

breakpoints scttered in the genomic region
are of uniwue size and genomic material in unrel inds


what is array comparative genomic hybridisation

seq genome on a chip
mix with sample
allow to hybridise
green = more sample than control
red = less sample than cotnrol
can be used for exome and genoome


are dup and del occur in equal number

in theory yes as production is reciprocal
but dup harder id
eg so far found 211 micro del syndromes vs 79 micro del`


what is the 11q22 micro dup syndrome gene compoents

pathological cnv
dev delay and behav defects
11 known genes in region
inc LAMTOR2/LMNA/SEMA4A present as pr complex dup probs imbalances it and why ptype patholgical


what diseases is the MTOR complex already associated with (MTOR= LAMTOR" of 11q22 dup syndrome assoc with)

autism spectrum disorders
therefore making the LAMTOR2 good candiate for the pathological ptype seen


what is the charcot marie tooth syndrome

dup of pmp22
the reciprocal deletion - hereditary neuropathy wit liability to pressure palsies


what important about the discovery of charcot marie tooth syndrome

id by aCGH
confirm by qPCR


what the length of microdeletion syndrome deletion

vary 1kb-100skb


what eg of single gene del syndrome

alagille syndrome


What the genetic cause of alagille syndrome

JAG1 deletion - defect notch singalling
point mut in JAG1 confirm is the gene inv
JAG1 a mut dom gene - haploinsufficieny cause diseas


what patho ptype assoc with alagille syndrome

liver disease
heart disease
eye and skeletal defects


what is contiguous ene del syndrome and give eg

ptype due to loss of several linked genes
common in x chr
X linked agammaglobinemia
- del of BTK and TIMM8A


what us segmental aneuploidy syndormes an eg of

special type of contiguous gene del syndrome with common occurence and recog ptype


give an eg of segmental aneuploidy syndormes

Digeorge and velocardiofacial syndrome
del of 22q.11.2


what special about digeorge syndorme

a 22q.11.2 deletion syndrome
have ptype but no known cause


22q.11.2 deletion syndrome how do they occur

aar of misparing of the lcr amd unequal crossing over in meiosis


what ptpe are assoc with 22q.11.2 deletion syndrome

cardiac defect - structural abn
immune defect - lack thymus
palate defect - musculare weakening
dev delay
psychologicla probs in later life


epidemology facts on 22q.11.2 deletion syndrome

no gender diff
no founder effect
FISH first use but probs under detected new techs reveal higher freq of atypical in the region than prev thought


what the gentic basis of 22q.11.2 deletion syndromes

haploinsufficiency of tbx1
causes sim ptype
tbx1 mut in pateint with the ptype but no del = confirms is this gene major inv
no ther gens attributed to ptype seen


what probems in study genetic of 22q.11.2 deletion syndrome

is patient variation in ptype = correlating genes and minor aspect of ptype difficult


what did mouse model show on the role of tbx1 in 22q.11.2 deletion syndrome

tbx1 norm expr in secondary heart field
which then develops into outflow tract
= area norm effected in the syndrome
tb1 norm act fgf8 to promote prolif and represses srf which control cell diff


what common heart defect result from 22q.11.2 deletion syndrome

trunucus arterious - aar of decr prolif of outflow tract
= failure of of to divide into aorta and
pulmonary vessels
interupted aortic arch - aar of lack of tbx1 in 2 heart field
no ncc prolif which norm
contrib to the arch formation
tetraology of fallot - complex heart malformations / dev cause unkown but defective dev of rhs of heart


what gene link to digeorge and why

a histtone acetyltransferase
ko results in tpye eg no thymus/cardia defect and celft palate/hypothyroid - similar to di george


what the molecular mechnaims behind the effect of moz mutants

mox imp in histone modification
in a moz mut there is less h3k9ac on tbx1 promoter (assoc with act)
and incr in h3k9me3 (assoc with repr) on teh tbx1 promoter
= so important for tbx1 act


what the ptype of 22q.11.2 dduplication

presence FISH rev
some healthy
some evidence of caridac defect
some other malform