DETECTION OF NUMEROUS Y-CHROMOSOME BIALLELIC POLYMORPHISMS BY DENATURING HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

Y chromosome haplotypes are particularly useful in deciphering human e volutionary history because they accentuate the effects of drift, migr ation, and range expansion. Significant acceleration of Y biallelic ma rker discovery and subsequent typing involving heteroduplex detection has been achieved by implementing an innovative and cost-efficient met hod called denaturing high-performance liquid chromatography (DHPLC). The power of the method resides in its sensitivity and ability to rapi dly compare amplified sequences in an automated manner. We have determ ined the allelic states of 22 Y polymorphisms; 19 of which are unrepor ted, in 718 diverse extant chromosomes; established haplotype frequenc ies; and deduced a phylogeny. All major geographic regions, including Eurasia, are characterized by mutations reflecting episodes of genetic drift and expansion, Most biallelic markers are localized regionally. However, some show wider dispersal and designate older, core haplotyp es. One transversion defines a major haplogroup that distinguishes a p reviously unknown deep, apparently non-African branch. It provides evi dence of an ancient bottleneck event. It is now possible to anticipate the inevitable detailed reconstruction of human Y chromosome genealog y based on several tens to even hundreds of these important polymorphi sms.