HLA alleles and haplotypes observed in 263 US families

Kazutoyo Osoegawa; Kalyan C. Mallempati; Sridevi Gangavarapu; Arisa Oki; Ketevan Gendzekhadze; Susana R. Marino; Nicholas K. Brown; Maria P. Bettinotti; Eric T. Weimer; Gonzalo Montero-Martín; Lisa E. Creary; Tamara A. Vayntrub; Chia Jung Chang; Medhat Askar; Steven J. Mack; Marcelo A. Fernández-Viña

doi:10.1016/j.humimm.2019.05.018

HLA alleles and haplotypes observed in 263 US families

Kazutoyo Osoegawa, Kalyan C. Mallempati, Sridevi Gangavarapu, Arisa Oki, Ketevan Gendzekhadze, Susana R. Marino, Nicholas K. Brown, Maria P. Bettinotti, Eric T. Weimer, Gonzalo Montero-Martín, Lisa E. Creary, Tamara A. Vayntrub, Chia Jung Chang, Medhat Askar, Steven J. Mack, Marcelo A. Fernández-Viña

School of Medicine

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	644-660
Number of pages	17
Journal	Human Immunology
Volume	80
Issue number	9
DOIs	https://doi.org/10.1016/j.humimm.2019.05.018
State	Published - Sep 2019

Keywords

Family
HLA haplotype
Linkage disequilibrium

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.1016/j.humimm.2019.05.018

Cite this

Osoegawa, K., Mallempati, K. C., Gangavarapu, S., Oki, A., Gendzekhadze, K., Marino, S. R., Brown, N. K., Bettinotti, M. P., Weimer, E. T., Montero-Martín, G., Creary, L. E., Vayntrub, T. A., Chang, C. J., Askar, M., Mack, S. J., & Fernández-Viña, M. A. (2019). HLA alleles and haplotypes observed in 263 US families. Human Immunology, 80(9), 644-660. https://doi.org/10.1016/j.humimm.2019.05.018

Osoegawa, K, Mallempati, KC, Gangavarapu, S, Oki, A, Gendzekhadze, K, Marino, SR, Brown, NK, Bettinotti, MP, Weimer, ET, Montero-Martín, G, Creary, LE, Vayntrub, TA, Chang, CJ, Askar, M, Mack, SJ & Fernández-Viña, MA 2019, 'HLA alleles and haplotypes observed in 263 US families', Human Immunology, vol. 80, no. 9, pp. 644-660. https://doi.org/10.1016/j.humimm.2019.05.018

@article{892f862af0be4a8fb7dfdf137ec24f71,

title = "HLA alleles and haplotypes observed in 263 US families",

abstract = "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.",

keywords = "Family, HLA haplotype, Linkage disequilibrium",

author = "Kazutoyo Osoegawa and Mallempati, {Kalyan C.} and Sridevi Gangavarapu and Arisa Oki and Ketevan Gendzekhadze and Marino, {Susana R.} and Brown, {Nicholas K.} and Bettinotti, {Maria P.} and Weimer, {Eric T.} and Gonzalo Montero-Mart{\'i}n and Creary, {Lisa E.} and Vayntrub, {Tamara A.} and Chang, {Chia Jung} and Medhat Askar and Mack, {Steven J.} and Fern{\'a}ndez-Vi{\~n}a, {Marcelo A.}",

note = "Funding Information: We thank the Stanford Blood Center for the support and promotion of the 17th IHIW endeavor, and Susan Twietmeyer for their tremendous administrative support of the 17th IHIW efforts. We also thank members of Histocompatibility, Immunogenetics & Disease Profiling Laboratory at the Stanford Blood Center, and A. Karl Kornel (Research Computing, Stanford University) for their technical support. We acknowledge the histocompatibility and immunogenetics community and the International HLA and Immunogenetics Workshop Council for their continued dedication to and support of the International Workshops. The work described here was supported by National Institutes of Health (NIH) National Institute of Allergy and Infectious Disease (NIAID) grant R01AI128775 (SM) and National Institute of Neurological Disorders and Stroke (NINDS) grant and U19NS095774 (GMM, LEC and MFV). The content is solely the responsibility of the authors and does not necessarily reflect the official views of the NIAID, NINDS, NIH or United States Government. Publisher Copyright: {\textcopyright} 2019 American Society for Histocompatibility and Immunogenetics",

year = "2019",

month = sep,

doi = "10.1016/j.humimm.2019.05.018",

language = "English (US)",

volume = "80",

pages = "644--660",

journal = "Human Immunology",

issn = "0198-8859",

publisher = "Elsevier Inc.",

number = "9",

}

TY - JOUR

T1 - HLA alleles and haplotypes observed in 263 US families

AU - Osoegawa, Kazutoyo

AU - Mallempati, Kalyan C.

AU - Gangavarapu, Sridevi

AU - Oki, Arisa

AU - Gendzekhadze, Ketevan

AU - Marino, Susana R.

AU - Brown, Nicholas K.

AU - Bettinotti, Maria P.

AU - Weimer, Eric T.

AU - Montero-Martín, Gonzalo

AU - Creary, Lisa E.

AU - Vayntrub, Tamara A.

AU - Chang, Chia Jung

AU - Askar, Medhat

AU - Mack, Steven J.

AU - Fernández-Viña, Marcelo A.

N1 - Funding Information: We thank the Stanford Blood Center for the support and promotion of the 17th IHIW endeavor, and Susan Twietmeyer for their tremendous administrative support of the 17th IHIW efforts. We also thank members of Histocompatibility, Immunogenetics & Disease Profiling Laboratory at the Stanford Blood Center, and A. Karl Kornel (Research Computing, Stanford University) for their technical support. We acknowledge the histocompatibility and immunogenetics community and the International HLA and Immunogenetics Workshop Council for their continued dedication to and support of the International Workshops. The work described here was supported by National Institutes of Health (NIH) National Institute of Allergy and Infectious Disease (NIAID) grant R01AI128775 (SM) and National Institute of Neurological Disorders and Stroke (NINDS) grant and U19NS095774 (GMM, LEC and MFV). The content is solely the responsibility of the authors and does not necessarily reflect the official views of the NIAID, NINDS, NIH or United States Government. Publisher Copyright: © 2019 American Society for Histocompatibility and Immunogenetics

PY - 2019/9

Y1 - 2019/9

N2 - 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.

AB - 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.

KW - Family

KW - HLA haplotype

KW - Linkage disequilibrium

UR - http://www.scopus.com/inward/record.url?scp=85067940966&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067940966&partnerID=8YFLogxK

U2 - 10.1016/j.humimm.2019.05.018

DO - 10.1016/j.humimm.2019.05.018

M3 - Article

C2 - 31256909

AN - SCOPUS:85067940966

SN - 0198-8859

VL - 80

SP - 644

EP - 660

JO - Human Immunology

JF - Human Immunology

IS - 9

ER -

HLA alleles and haplotypes observed in 263 US families

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this