Applied Research of Distinguishing Similar Y-STR Haplotypes by Y Chromosome Complete Sequencing

Background: To explore a technical method to distinguish similar Y-STR haplotypes and its value in deducing the differentiation the males in paternal line, we used a complete genome sequence of Y chromosome using streptavidin–biotin magnetic particle-based capture methodology (Y chromosome liquid phase probe capture next generation sequencing technique (NGS)) to detect male individuals with similar Y-STR haplotypes. Based on our independently developed mathematical model and the new topological structure of Y chromosome mutation sites as well as haplogroups and pedigree trees updated by the International Society of Genealogy (ISOGG) every year, we distinguished the coancestry of male individuals with similar Y-STR haplotypes and Results: Identifying differences between the judgment results of Y full sequencing and the pedigree survey results allowed for the estimation whether the individuals have close relation within 3~5 generations or not. Y chromosome liquid phase probe capture NGS technique could capture the 16M region and effectively analyze tens of thousands of Y-SNP loci. Among them, the coancestry obtained by analysis of 8 sample cases was consistent with the actual total case time obtained by family investigation. Conclusions: Detecting the Y-STR haplotype similarity between male individuals and conducting the previously reported mathematical model analysis by using Y chromosome liquid phase probe capture NGS technology can uncover the coancestry of the different male individuals. These results provide the foundation for further investigation of the similar Y-STR haplotype males in the Y-STR database.

INCREASING POWER BY USING HAPLOTYPE SIMILARITY IN A MULTIMARKER TRANSMISSION/DISEQUILIBRIUM TEST

It is already known that power in multimarker transmission/disequilibrium tests may improve with the number of markers as some associations may require several markers to be captured. However, a mechanism such as haplotype grouping must be used to avoid incremental complexity with the number of markers. 2G, a state-of-the-art transmission/disequilibrium test, implements this mechanism to its maximum extent by grouping haplotypes into only two groups, high and low-risk haplotypes, so that the test has only one degree of freedom regardless of the number of markers. The test checks whether those haplotypes more often transmitted from parents to offspring are truly high-risk haplotypes. In this paper we use haplotype similarity as prior knowledge to classify haplotypes as high or low risk ones and start with those haplotypes in which the prior will have lower impact i.e. those with the largest differences between transmission and non-transmission counts. If their counts are very different, the prior knowledge has little effect and haplotypes are classified as low or high risk as 2G does. We show a substantial gain in power achieved by this approach, in both simulation and real data sets.