MOLECULAR ANALYSIS OF RECOMBINATION IN A FAMILY WITH DUCHENNE MUSCULAR-DYSTROPHY AND A LARGE PERICENTRIC X-CHROMOSOME INVERSION

It has been demonstrated in animal studies that, in animals heterozygo us for pericentric chromosomal inversions, loop formation is greatly r educed during meiosis. This results in absence of recombination within the inverted segment, with recombination seen only outside the invers ion. A recent study in yeast has shown that telomeres, rather than cen tromeres, lead in chromosome movement just prior to meiosis and may be involved in promoting recombination. We studied by cytogenetic analys is and DNA polymorphisms the nature of meiotic recombination in a thre e-generation family with a large pericentric X chromosome inversion, i nv(X)(p21.1q26), in which Duchenne muscular dystrophy (DMD) was cosegr egating with the inversion. On DNA analysis there was no evidence of m eiotic recombination between the inverted and normal X chromosomes in the inverted segment. Recombination was seen at the telomeric regions, Xp22 and Xq27-28. No deletion or point mutation was found on analysis of the DMD gene. On the basis of the FISH results, we believe that th e X inversion is the mutation responsible for DMD in this family. Our results indicate that (1) pericentric X chromosome inversions result i n reduction of recombination between the normal and inverted X chromos omes; (2) meiotic X chromosome pairing in these individuals is likely initiated at the telomeres; and (3) in this family DMD is caused by th e pericentric inversion.