title: Polymorphisms of the 22q11.2 breakpoint region influence the frequency of de novo constitutional t(11;22)s in sperm.
abstract: The constitutional t(11;22) is the most frequent recurrent non-Robertsonian translocation in humans, the breakpoints of which are located within palindromic AT-rich repeats on 11q23 and 22q11 (PATRR11 and PATRR22). Genetic variation of the PATRR11 was found to affect de novo t(11;22) translocation frequency in sperm derived from normal healthy males, suggesting the hypothesis that polymorphisms of the PATRR22 might also influence the translocation frequency. Although the complicated structure of the PATRR22 locus prevented determining the genotype of the PATRR22 in each individual, genotyping of flanking markers as well as identification of rare variants allowed us to demonstrate an association between the PATRR22 allele type and the translocation frequency. We found that size and symmetry of the PATRR22 affect the de novo translocation frequency, which is lower for the shorter or more asymmetric versions. These data lend support to our hypothesis that the PATRRs form secondary structures in the nucleus that induce genomic instability leading to the recurrent translocation.
authors.affiliation: Institute for Comprehensive Medical Science, Fujita Health University, Aichi, Japan.
authors.forename: Maoqing
authors.initials: M
authors.lastname: Tong
authors.forename: Takema
authors.initials: T
authors.lastname: Kato
authors.forename: Kouji
authors.initials: K
authors.lastname: Yamada
authors.forename: Hidehito
authors.initials: H
authors.lastname: Inagaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kogo
authors.forename: Tamae
authors.initials: T
authors.lastname: Ohye
authors.forename: Makiko
authors.initials: M
authors.lastname: Tsutsumi
authors.forename: Jieru
authors.initials: J
authors.lastname: Wang
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Emanuel
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
mesh_terms: D020856:AT Rich Sequence / Q000235:genetics; D000483:Alleles; D019457:Chromosome Breakage; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D013094:Spermatozoa; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D004247:DNA
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