A novel method for haplotype phasing in families after joint estimation of recombination fraction and linkage disequilibrium is developed. Results from Monte Carlo computer simulations show that the newly developed E....A novel method for haplotype phasing in families after joint estimation of recombination fraction and linkage disequilibrium is developed. Results from Monte Carlo computer simulations show that the newly developed E.M. algorithm is accurate if true recombination fraction is 0 even for single families of relatively small sizes. Estimates of recombination fraction and linkage disequilibrium were 0.00 （SD 0.00） and 0.19 （SD 0.03） for simulated recombination fraction and linkage disequilibrium of 0.00 and 0.20, respectively. A genome fragmentation phasing strategy was developed and used for phasing haplotypes in a sire and 36 progeny using the 50 k Illumina BeadChip by： a） estimation of the recombination fraction and LD in consecutive SNPs using family information, b） linkage analyses between fragments, c） phasing of haplotypes in parents and progeny and in following generations. Homozygous SNPs in progeny allowed determination of paternal fragment inheritance, and deduction of SNP sequence information of haplotypes from dams. The strategy also allowed detection of genotyping errors. A total of 613 recombination events were detected after linkage analysis was carried out between fragments. Hot and cold spots were identified at the individual （sire level）. SNPs for which the sire and calf were heterozygotes became informative （over 90%） after the phasing of haplotypes. Average of regions of identity between half-sibs when comparing its maternal inherited haplotypes （with at least 20 SNP） in common was 0.11 with a maximum of 0.29 and a minimum of 0.05. A Monte-Carlo simulation of BTA1 with the same linkage disequilibrium structure and genetic linkage as the cattle family yielded a 99.98 and 99.94% of correct phases for informative SNPs in sire and calves, respectively.展开更多
Hearing loss is the most common neurosensory deficit.It results froma variety of heritable and acquired causes and is linked to multiple deleterious effects on a child’s development that can be ameliorated by prompt ...Hearing loss is the most common neurosensory deficit.It results froma variety of heritable and acquired causes and is linked to multiple deleterious effects on a child’s development that can be ameliorated by prompt identification and individualized therapies.Diagnosing hearing loss in newborns is challenging,especially in mild or progressive cases,and its management requires a multidisciplinary team of healthcare providers comprising audiologists,pediatricians,otolaryngologists,and genetic counselors.While physiologic newborn hearing screening has resulted in earlier diagnosis of hearing loss than ever before,a growing body of knowledge supports the concurrent implementation of genetic and cytomegalovirus testing to offset the limitations inherent to a singular screening modality.In this review,we discuss the contemporary role of screening for hearing loss in newborns as well as future directions in its diagnosis and treatment.展开更多
基金support from a Marie Curie International Reintegration Grant from the European Union,project no.PIRG08-GA-2010-277031 "SelectionForWelfare"LGR and WMR acknowledge support from project AGL2012-39137
文摘A novel method for haplotype phasing in families after joint estimation of recombination fraction and linkage disequilibrium is developed. Results from Monte Carlo computer simulations show that the newly developed E.M. algorithm is accurate if true recombination fraction is 0 even for single families of relatively small sizes. Estimates of recombination fraction and linkage disequilibrium were 0.00 （SD 0.00） and 0.19 （SD 0.03） for simulated recombination fraction and linkage disequilibrium of 0.00 and 0.20, respectively. A genome fragmentation phasing strategy was developed and used for phasing haplotypes in a sire and 36 progeny using the 50 k Illumina BeadChip by： a） estimation of the recombination fraction and LD in consecutive SNPs using family information, b） linkage analyses between fragments, c） phasing of haplotypes in parents and progeny and in following generations. Homozygous SNPs in progeny allowed determination of paternal fragment inheritance, and deduction of SNP sequence information of haplotypes from dams. The strategy also allowed detection of genotyping errors. A total of 613 recombination events were detected after linkage analysis was carried out between fragments. Hot and cold spots were identified at the individual （sire level）. SNPs for which the sire and calf were heterozygotes became informative （over 90%） after the phasing of haplotypes. Average of regions of identity between half-sibs when comparing its maternal inherited haplotypes （with at least 20 SNP） in common was 0.11 with a maximum of 0.29 and a minimum of 0.05. A Monte-Carlo simulation of BTA1 with the same linkage disequilibrium structure and genetic linkage as the cattle family yielded a 99.98 and 99.94% of correct phases for informative SNPs in sire and calves, respectively.
基金This project was supported by NIH-NIDCD(Grants No.R01 DC002842,DC012049,and DC017955)(RJHS)NIH-NIDCD(Grant No.5T32DC000040)(RKT).
文摘Hearing loss is the most common neurosensory deficit.It results froma variety of heritable and acquired causes and is linked to multiple deleterious effects on a child’s development that can be ameliorated by prompt identification and individualized therapies.Diagnosing hearing loss in newborns is challenging,especially in mild or progressive cases,and its management requires a multidisciplinary team of healthcare providers comprising audiologists,pediatricians,otolaryngologists,and genetic counselors.While physiologic newborn hearing screening has resulted in earlier diagnosis of hearing loss than ever before,a growing body of knowledge supports the concurrent implementation of genetic and cytomegalovirus testing to offset the limitations inherent to a singular screening modality.In this review,we discuss the contemporary role of screening for hearing loss in newborns as well as future directions in its diagnosis and treatment.
