An efficient rule-based algorithm is presented for haplotype inference from general pedigree genotype data, with the assumption of no recombination. This algorithm generalizes previous algorithms to handle the cases w...An efficient rule-based algorithm is presented for haplotype inference from general pedigree genotype data, with the assumption of no recombination. This algorithm generalizes previous algorithms to handle the cases where some pedigree founders are not genotyped, provided that for each nuclear family at least one parent is genotyped and each non-genotyped founder appears in exactly one nuclear family. The importance of this generalization lies in that such cases frequently happen in real data, because some founders may have passed away and their genotype data can no longer be collected. The algorithm runs in O（m^3n^3） time, where m is the number of single nucleotide polymorphism （SNP） loci under consideration and n is the number of genotyped members in the pedigree. This zero-recombination haplotyping algorithm is extended to a maximum parsimoniously haplotyping algorithm in one whole genome scan to minimize the total number of breakpoint sites, or equivalently, the number of maximal zero-recombination chromosomal regions. We show that such a whole genome scan haplotyping algorithm can be implemented in O（m^3n^3） time in a novel incremental fashion, here m denotes the total number of SNP loci along the chromosome.展开更多
To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic an...To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors （P 〈 0.001） with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA （cross-section area）, W （sub-periosteal diameter）, Z （section modulus） and CT （cortical thickness） except between TBFM and BR （buckling ratio）. The peak bivariate LOD scores were 3.23 （20q12）, 2.47 （20p11）, 3.19 （6q27）, 1.68 （20p12）, and 2.47 （7q11） for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM ＆ Z in the female sub-population, and 6q27 and 17q11 had coincident link- ages for TBFM ＆ CSA and TBFM ＆ Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.展开更多
基金supported in part by AARI,AICML,ALIDF,iCORE,and NSERC
文摘An efficient rule-based algorithm is presented for haplotype inference from general pedigree genotype data, with the assumption of no recombination. This algorithm generalizes previous algorithms to handle the cases where some pedigree founders are not genotyped, provided that for each nuclear family at least one parent is genotyped and each non-genotyped founder appears in exactly one nuclear family. The importance of this generalization lies in that such cases frequently happen in real data, because some founders may have passed away and their genotype data can no longer be collected. The algorithm runs in O（m^3n^3） time, where m is the number of single nucleotide polymorphism （SNP） loci under consideration and n is the number of genotyped members in the pedigree. This zero-recombination haplotyping algorithm is extended to a maximum parsimoniously haplotyping algorithm in one whole genome scan to minimize the total number of breakpoint sites, or equivalently, the number of maximal zero-recombination chromosomal regions. We show that such a whole genome scan haplotyping algorithm can be implemented in O（m^3n^3） time in a novel incremental fashion, here m denotes the total number of SNP loci along the chromosome.
基金supported by grants from NIH in USA (No. K01 AR02170-01, R01 AR45349-01, R01 GM60402-01 A1, R01 AG026564-01A2, and R21 AG027110-01A1)the Natural Science Foundation o China (NSFC) (No. 30600364)The genotyping experiment was performed by Marshfield Center for Medical Genetics and supported by NHLB Mammalian Genotyping Service (Contract No. HV48141)
文摘To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors （P 〈 0.001） with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA （cross-section area）, W （sub-periosteal diameter）, Z （section modulus） and CT （cortical thickness） except between TBFM and BR （buckling ratio）. The peak bivariate LOD scores were 3.23 （20q12）, 2.47 （20p11）, 3.19 （6q27）, 1.68 （20p12）, and 2.47 （7q11） for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM ＆ Z in the female sub-population, and 6q27 and 17q11 had coincident link- ages for TBFM ＆ CSA and TBFM ＆ Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.
