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HLA alleles and haplotypes observed in 263 US families
- Osoegawa, Kazutoyo;
- Mallempati, Kalyan C;
- Gangavarapu, Sridevi;
- Oki, Arisa;
- Gendzekhadze, Ketevan;
- Marino, Susana R;
- Brown, Nicholas K;
- Bettinotti, Maria P;
- Weimer, Eric T;
- Montero-Martín, Gonzalo;
- Creary, Lisa E;
- Vayntrub, Tamara A;
- Chang, Chia-Jung;
- Askar, Medhat;
- Mack, Steven J;
- Fernández-Viña, Marcelo A
- et al.
Published Web Location
https://doi.org/10.1016/j.humimm.2019.05.018Abstract
The 17th International HLA and Immunogenetics Workshop (IHIW) conducted a project entitled "The Study of Haplotypes in Families by NGS HLA". We investigated the HLA haplotypes of 1017 subjects in 263 nuclear families sourced from five US clinical immunogenetics laboratories, primarily as part of the evaluation of related donor candidates for hematopoietic stem cell and solid organ transplantation. The parents in these families belonged to five broad groups - African (72 parents), Asian (115), European (210), Hispanic (118) and "Other" (11). High-resolution HLA genotypes were generated for each subject using next-generation sequencing (NGS) HLA typing systems. We identified the HLA haplotypes in each family using HaplObserve, software that builds haplotypes in families by reviewing HLA allele segregation from parents to children. We calculated haplotype frequencies within each broad group, by treating the parents in each family as unrelated individuals. We also calculated standard measures of global linkage disequilibrium (LD) and conditional asymmetric LD for each ethnic group, and used untruncated and two-field allele names to investigate LD patterns. Finally we demonstrated the utility of consensus DNA sequences in identifying novel variants, confirming them using HLA allele segregation at the DNA sequence level.
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