Immune diversity sheds light on missing variation in worldwide genetic diversity panels

Abi-Rached, Laurent; Gouret, Philippe; Yeh, Jung-Hua; Cristofaro, Julie Di; Pontarotti, Pierre; Picard, Christophe; Paganini, Julien

doi:10.1371/journal.pone.0206512

Cited by 60 publications

(79 citation statements)

References 25 publications

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“…Sample size of some Dutch Landrace lines used in this study were relatively small, due to limited availability of samples, and differed between lines, ranging from 11 samples for the lines FL and FZ lines to 49 for the DL line. Small sample size can lead to incorrect estimates of allele frequencies [27] and a proportion of genetic diversity present in the lines may remain undetected. Nevertheless, the results showed that the sampled animals formed genetic clusters that corresponded to their line designations (Fig.…”

Section: Discussionmentioning

confidence: 99%

Impact of merging commercial breeding lines on the genetic diversity of Landrace pigs

et al. 2019

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BackgroundThe pig breeding industry has undergone a large number of mergers in the past decades. Various commercial lines were merged or discontinued, which is expected to reduce the genetic diversity of the pig species. The objective of the current study was to investigate the genetic diversity of different former Dutch Landrace breeding lines and quantify their relationship with the current Dutch Landrace breed that originated from these lines.ResultsPrincipal component analysis clearly divided the former Landrace lines into two main clusters, which are represented by Norwegian/Finnish Landrace lines and Dutch Landrace lines. Structure analysis revealed that each of the lines that are present in the Dutch Gene bank has a unique genetic identity. The current Dutch Landrace breed shows a high level of admixture and is closely related to the six former lines. The Dumeco N-line, which is conserved in the Dutch Gene bank, is poorly represented in the current Dutch Landrace. All seven lines (the six former and the current line) contribute almost equally to the genetic diversity of the Dutch Landrace breed. As expected, the current Dutch Landrace breed comprises only a small proportion of unique genetic diversity that was not present in the other lines. The genetic diversity level, as measured by Eding’s core set method, was equal to 0.89 for the current Dutch Landrace breed, whereas total genetic diversity across the seven lines, measured by the same method, was equal to 0.99.ConclusionsThe current Dutch Landrace breed shows a high level of admixture and is closely related to the six former Dutch Landrace lines. Merging of commercial Landrace lines has reduced the genetic diversity of the Landrace population in the Netherlands, although a large proportion of the original variation is maintained. Thus, our recommendation is to conserve breeding lines in a gene bank before they are merged.

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Section: Discussionmentioning

confidence: 99%

Impact of merging commercial breeding lines on the genetic diversity of Landrace pigs

et al. 2019

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“…We built a multi-ancestry imputation model for HLA-A, -B, -C, -DQB1, and -DRB1 with two-field level of resolution using the 1000 Genomes phase III (2,504 individuals) as a reference panel (31,32). We selected SNPs within the MHC region which are present in both the TM array (10,711 SNPs) and HumanOmin2.5 (9,187 SNPs).…”

Section: Hla Imputationmentioning

confidence: 99%

How Ancestry Influences the Chances of Finding Unrelated Donors: An Investigation in Admixed Brazilians

et al. 2020

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associated with reduced chances of finding a match (up to 60% reduction). Finally, we document that the strongest reduction in chances of finding a match is associated with having an MHC region of exclusively African ancestry (up to 75% reduction). We apply our findings to a specific condition, for which there is a clinical indication for transplantation: sickle-cell disease. We show that the increased African ancestry in patients with this disease leads to reduced chances of finding a match, when compared to the remainder of the sample, without the condition. Our results underscore the influence of ancestry on chances of finding compatible HLA matches, and indicate that efforts guided to increasing the African component of registries are necessary.

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“…RNA sequencing data were analyzed using PolyPheMe software specially designed for HLA NGS data analysis (Xegen, France) for which accuracy was assessed at 99.3% (10,32,33). This software is based on a specific strategy to avoid bias raised by the use of a unique genome as a reference for HLA NGS data mapping (34)(35)(36).…”

Section: Hla-h Transcriptional Expression In Cell Line From the 1000 mentioning

confidence: 99%

HLA-H: Transcriptional Activity and HLA-E Mobilization

et al. 2020

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Little attention is paid to pseudogenes from the highly polymorphic HLA genetic region. The pseudogene HLA-H is defined as a non-functional gene because it is deleted at different frequencies in humans and because it encodes a potentially non-functional truncated protein. However, different studies have shown HLA-H transcriptional activity. We formerly identified 13 novel HLA-H alleles, including the H * 02:07 allele, which reaches 19.6% in East Asian populations and encodes a full-length HLA protein. The aims of this study were to explore the expression and possible function of the HLA-H molecule. HLA-H may act as a transmembrane molecule and/or indirectly via its signal peptide by mobilizing HLA-E to the cell surface. We analyzed HLA-H RNA expression in Peripheral Blood Mononuclear Cells (PBMC), Human Bronchial Epithelial Cells (HBEC), and available RNA sequencing data from lymphoblastoid cell lines, and we looked to see whether HLA-E was mobilized at the cell surface by the HLA-H signal peptide. Our data confirmed that HLA-H is transcribed at similar levels to HLA-G. We characterized a hemizygous effect in HLA-H expression, and expression differed according to HLA-H alleles; most interestingly, the HLA-H * 02:07 allele had the highest level of mRNA expression. We showed that HLA-H signal peptide incubation mobilized HLA-E molecules at the cell surface of T-Lymphocytes, monocytes, B-Lymphocytes, and primary epithelial cells. Our results suggest that HLA-H may be functional but raises many biological issues that need to be addressed.

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Immune diversity sheds light on missing variation in worldwide genetic diversity panels

Cited by 60 publications

References 25 publications

Impact of merging commercial breeding lines on the genetic diversity of Landrace pigs

Impact of merging commercial breeding lines on the genetic diversity of Landrace pigs

How Ancestry Influences the Chances of Finding Unrelated Donors: An Investigation in Admixed Brazilians

HLA-H: Transcriptional Activity and HLA-E Mobilization

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