Study of the meiotic segregation of chromosome 7 with a paracentric inversion in spermatosoa of a heterozygous carrier

对杂合子携带者精子中具有臂间倒位的7号染色体的减数分裂分离进行研究

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Abstract

A paracentric inversion (PAI) is a rare type of balanced intrachromosomal structural rearrangement. Heterozygotes for PAI are usually phenotypically normal, but the presence of the inversion may occasionally lead to synapsis and recombination disruptions during meiosis. PAI can be responsible for the production of recombinant chromosomes and unbalanced gametes. The risks associated with the birth of a child with chromosomal imbalances due to the generation of unbalanced crossover gametes is considered to be low. Nonetheless, viable offspring with intellectual disabilities and/or congenital abnormalities, as well as early miscarriages, stillbirth and infertility in heterozygous carriers of PAI have been described. Paracentric inversions may arise on various chromosomes. PAI with breakpoints on the long arm of chromosome 7 is among the most prevalent ones in humans. To assess the meiotic behavior of abnormal chromosome 7, as well as the empirical risk of producing gametes with recombinant chromosomes, the sperm FISH analysis of a male heterozygous carrier of inv(7)(q11.23q22) was performed. The percentage of recombinant sperms was 0.7 % and chromosomal imbalance was represented as reciprocal breakage products of a dicentric chromosome 7. Notably, spermatozoa with a dicentric chromosome 7 were not observed, which confirms its instability during meiosis I. Meiotic segregation analysis in the heterozygous carrier of inv(7)(q11.23q22) revealed a predominant formation of gametes containing either the inverted or the intact chromosome 7, occurring at frequencies of 52.2 and 47.8 %, respectively. This report is the first study providing a detailed description of meiotic segregation patterns of inv(7)(q11.23q22) by using a sperm FISH approach. Recombinant gamete formation confirms the occurrence of crossing-over within the inversion loop. Consequently, the individual risk of generating gametes (and subsequent zygotes) with chromosome 7 imbalance for this heterozygous carrier remains low.

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