Sperm-FISH analysis in a pericentric chromosome 1 inversion, 46,XY,inv(1)(p22q42), associated with infertility

Abstract

No phenotypic effect is observed in most inversion heterozygotes. However, reproductive risks may occur in the form of infertility, spontaneous abortions or chromosomally unbalanced children as a consequence of meiotic recombination between inverted and non-inverted chromosomes. An odd number of crossovers within the inverted segment results in gametes bearing recombinant chromosomes with a duplication of the region outside of the inversion segment of one arm and a deletion of the terminal segment of the other arm [dup(p)/del(q) and del(p)/dup(q)]. Using fluorescence in-situ hybridization (FISH), the chromosome segregation of a pericentric inversion of chromosome 1 was studied in spermatozoa of a inv(1)(p22q42) heterozygous carrier. Three-colour FISH was performed on sperm samples using a probe mixture consisting of chromosome 1p telomere-specific probe, chromosome 1q telomere-specific probe and chromosome 18 centromere-specific alpha satellite DNA probe. The frequency of the non-recombinant product was 80.1%. The frequencies of the two types of recombinants carrying a duplication of the short arm and a deletion of the long arm, and vice versa, were respectively 7.6 and 7.2%, and these frequencies were not statistically significant from the expected ratio of 1:1. Sperm-FISH allows the further understanding of segregation patterns and their effect on reproductive failure and allows an accurate genetic counselling.

Male Meiotic Segregation Analyses of Peri- and Paracentric Inversions in the Pig Species

“…This could partly explain the differences pointed out between the 2 species. Otherwise, in the case of very large inversions, it has been postulated [Anton et al, 2005;Chantot-Bastaraud et al, 2007] that synapsis of the inverted region with its homologous non-inverted segment prevails over pairing of the terminal segments, and that the regions outside the inversion may remain unpaired or aligned through heterosynapsis. This is consistent with the high proportions of recombinant gametes reported in the cases of In blue: data from the present study (inversions of chromosome 1).…”

“…Although many cases of inversions have been described in man [Madan, 1995;Pettenati et al, 1995;Anton et al, 2005;Morel et al, 2007] as well as in pigs [Ducos et al, 2007], only few studies have reported on the analysis of chromosome segregation of pericentric [Anton et al, 2005;Malan et al, 2006;Chantot-Bastaraud et al, 2007;Morel et al, 2007;Caer et al, 2008] or paracentric [Devine et al, 2000;Anton et al, 2006;Bhatt et al, 2007Bhatt et al, , 2009Vialard et al, 2007] inversions. Fluorescent in situ hybridization on decondensed sperm nuclei (sperm FISH) using a combination of telomeric probes has become the state-of-the-art technique to assess the segregation patterns of inversions in man [Anton et al, 2007;Vialard et al, 2007;Caer et al, 2008].…”

Centromeres in cell division, evolution, nuclear organization and disease

“…Centric breakage and fusion has been observed in Robertsonian translocation chromosomes of wheat and rye . Pericentric inversions in humans are often associated with decreased male fertility [Collodel et al, 2006;Chantot-Bastaraud et al, 2007, for review, see Anton et al, 2005, cancer [Mathew et al, 2002;Anelli et al, 2005;Pedrazzini et al, 2006], mental retardation [Ramadevi et al, 2002;Ulucan et al, 2006] and other diseases such as: [epilepsy: Grosso et al, 2004;cleft lip: Beiraghi et al, 2003; schizophrenia and learning disability: Hampson et al, 1999]. Such inversions may also be associated with duplications and deletions [López-Exposito et al, 2006;Patil and Phadke, 2007].…”

Different segregation patterns in five carriers due to a pericentric inversion of chromosome 1

“…To date, few studies have analyzed the segregation products on the sperm nuclei using fluorescence in situ hybridization (FISH) in the case of pericentric inversion [Anton et al 2002;Anton et al 2006;Bernicot et al 2010;Caer et al 2008;Chantot-Bastaraud et al 2007;Malan et al 2006;Mikhaail-Philips et al 2004;Mikhaail-Philips et al 2005]. The frequency of the two abnormal gametes ((dup p/ del q and del p/dup q) was highly variable from 0% to 37.85%.…”