AN INDEX MARKER MAP OF CHROMOSOME-9 PROVIDES STRONG EVIDENCE FOR POSITIVE INTERFERENCE

An index marker map of chromosome 9 has been constructed using the Cen tre d'Etude du Polymorphisme Humain reference pedigrees. The map compr ises 26 markers, with a maximum intermarker interval of 13.1 cM and on ly two intervals >10 cM. Placement of all but one marker into the map was achieved with >10,000:1 odds. The sex-equal length is 151 cM, with male length of 121 cM and female length of 185 cM. The map extends to within 2%-3% of physical length at the telomeres, and its coverage th erefore is expected to be within 20-30 cM of full map length. The mark ers are all of the GT/CA repeat type and have average heterozygosity . 77, with a range of .60-.89. The map shows both marked contraction of genetic distance relative to physical distance in the pericentromeric region and expansion in the telomeric regions. Genotypic data were car efully examined for errors by using the crossover routine of the progr am DATAMAN. Five new mutations were observed among 17,316 meiotic even ts examined. There were two double-crossover events occurring within a n interval of 0-10 cM, and another eight were observed within an inter val of 10-20 cM. Many of these could be due to additional mutational e vents in which one parental allele converted to the other by either ge ne conversion or random strand slippage. When there was no correction for these possible mutational events, the number of crossovers display ed by the maternal and paternal chromosomes was significantly differen t (P<.001) from that predicted by the Poisson distribution, which woul d be expected in the absence of interference. In addition, the observe d crossover distribution for paternally derived chromosomes was simila r to that predicted from cytogenetic chiasma frequency observations. I n all, the data strongly support the occurrence of strong positive int erference on human chromosome 9 and suggest that flanking markers at a n interval of less than or equal to 20 cM are generally sufficient for disease gene inheritance predictions in presymptomatic genetic counse ling by Linkage analysis.