Analysis of meiotic recombination in 22q11.2, a region that frequently undergoes deletions and duplications

Abstract

Background: The 22q11.2 deletion syndrome is the most frequent genomic disorder with an estimated frequency of 1/4000 live births. The majority of patients (90%) have the same deletion of 3 Mb (Typically Deleted Region, TDR) that results from aberrant recombination at meiosis between region specific low-copy repeats (LCRs).

Cognitive, Behavioural and Psychiatric Phenotype in 22q11.2 Deletion Syndrome

“…1). This is about equally likely to occur in spermatogenesis or oogenesis Torres-Juan et al 2007). Up to 90% of recombination events occur between LCRs A and D giving rise to the common 3 Mb deletion (Shaikh et al 2000).…”

A child with features of Goldenhar syndrome and a novel 1.12 Mb deletion in 22q11.2 by cytogenetics and oligonucleotide array CGH: Is this a candidate region for the syndrome?

“…However, the proximal end (20,100,000-20,500,000) of the deletion contains 9 genes (HIC2, LOC220686, UBE2L3, LOC150223, CCDC116, SDF2L1, PPPIL2, YPEL1, and MAPK1), which were not deleted in >2000 healthy control individuals [http://projects.tcag.ca/variation/]. This deletion (20,128,246,612) is within a 22q.11.2 region that has low copy repeats (LCRs) and frequently undergoes deletions and duplications [Torres-Juan et al, 2007]. Specifically, the proximal end of this deletion involves 777,241,670) and the distal end is in an interval between LCR22-4 and LCR22-5 [Torres-Juan et al, 2007].…”

“…This deletion (20,128,246,612) is within a 22q.11.2 region that has low copy repeats (LCRs) and frequently undergoes deletions and duplications [Torres-Juan et al, 2007]. Specifically, the proximal end of this deletion involves 777,241,670) and the distal end is in an interval between LCR22-4 and LCR22-5 [Torres-Juan et al, 2007]. It is possible that the 22q LCRs may have played a role for this deletion to occur, and if so we may expect to observe recurrence of this deletion in other patients.…”

Distinct karyotypes in two offspring of a man with jumping translocation karyotype 45,XY,der(16)t(16;22)(q24;q11.2), −22 [59]/45,XY,der(1)t(1;22)(p36;q11.2), −22 [11]/45,XY,der(22)t(22;22)(p13;q11.2), −22 [10]

“…LCRs constitute $5% of the human genome and are 10-400 kb DNA blocks that show more than 95% identity between copies and can be responsible for genomic instability [Torres-Juan et al, 2007]. Nonallelic homologous recombination between LCRs during meiosis can lead to the chromosomal rearrangements responsible for many genomic disorders.…”