Sequence Variation and Haplotype Structure at the HumanHFELocus

AbstractThe HFE locus encodes an HLA class-I-type protein important in iron regulation and segregates replacement mutations that give rise to the most common form of genetic hemochromatosis. The high frequency of one disease-associated mutation, C282Y, and the nature of this disease have led some to suggest a selective advantage for this mutation. To investigate the context in which this mutation arose and gain a better understanding of HFE genetic variation, we surveyed nucleotide variability in 11.2 kb encompassing the HFE locus and experimentally determined haplotypes. We fully resequenced 60 chromosomes of African, Asian, or European ancestry as well as one chimpanzee, revealing 41 variable sites and a nucleotide diversity of 0.08%. This indicates that linkage to the HLA region has not substantially increased the level of HFE variation. Although several haplotypes are shared between populations, one haplotype predominates in Asia but is nearly absent elsewhere, causing higher than average genetic differentiation among the three major populations. Our samples show evidence of intragenic recombination, so the scarcity of recombination events within the C282Y allele class is consistent with selection increasing the frequency of a young allele. Otherwise, the pattern of variability in this region does not clearly indicate the action of positive selection at this or linked loci.

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Adaptive Admixture of HLA class I Allotypes Enhanced Genetically Determined Strength of Natural Killer Cells in East Asians

Molecular Biology and Evolution ◽

10.1093/molbev/msab053 ◽

2021 ◽

Author(s):

Zhihui Deng ◽

Jianxin Zhen ◽

Genelle F Harrison ◽

Guobin Zhang ◽

Rui Chen ◽

...

Keyword(s):

Natural Killer ◽

High Frequency ◽

Nk Cell ◽

Killer Cell ◽

Hla Class I ◽

Class I ◽

Telomeric Region ◽

East Asians ◽

Cell Functions ◽

Specific Receptors

Abstract Human natural killer (NK) cells are essential for controlling infection, cancer and fetal development. NK cell functions are modulated by interactions between polymorphic inhibitory killer cell immunoglobulin-like receptors (KIR) and polymorphic HLA-A, -B and -C ligands expressed on tissue cells. All HLA-C alleles encode a KIR ligand and contribute to reproduction and immunity. In contrast, only some HLA-A and -B alleles encode KIR ligands and they focus on immunity. By high-resolution analysis of KIR and HLA-A, -B and -C genes, we show that the Chinese Southern Han are significantly enriched for interactions between inhibitory KIR and HLA-A and -B. This enrichment has had substantial input through population admixture with neighboring populations, who contributed HLA class I haplotypes expressing the KIR ligands B*46:01 and B*58:01, which subsequently rose to high frequency by natural selection. Consequently, over 80% of Southern Han HLA haplotypes encode more than one KIR ligand. Complementing the high number of KIR ligands, the Chinese Southern Han KIR locus combines a high frequency of genes expressing potent inhibitory KIR, with a low frequency of those expressing activating KIR. The Southern Han centromeric KIR region encodes strong, conserved, inhibitory HLA-C specific receptors, and the telomeric region provides a high number and diversity of inhibitory HLA-A and -B specific receptors. In all these characteristics, the Chinese Southern Han represent other East Asians, whose NK cell repertoires are thus enhanced in quantity, diversity and effector strength, likely augmenting resistance to endemic viral infections.

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Transduction mechanisms of bacteriophage ε15I. General properties of the system

Genetics Research ◽

10.1017/s0016672300012362 ◽

1971 ◽

Vol 18 (1) ◽

pp. 9-19 ◽

Cited By ~ 6

Author(s):

R. W. Hedges

Keyword(s):

High Frequency ◽

Genetic Material ◽

Recipient Strain ◽

The Other ◽

Donor Strain ◽

General Properties ◽

Show Evidence ◽

Transduction Mechanisms ◽

Defective Prophage

SUMMARYBacteriophageεγis capable of transduction both by replacement of a genetic segment of the recipient by the homologous genetic material from the donor strain and by the formation of defective transducing particles capable of lysogenizing the recipient strain ofS. anatum.The isolation of strains carrying such prophages, which have incorporated the lactose or arabinose operons, is reported. Lysogenic strains, carrying both normal and defective transducing prophage, form high-frequency transducing lysates. Other strains, carrying only defective prophage, show evidence that the association of prophage genes and transduced materials is stable since the loss of one frequently entails loss of the other.

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Multiple mechanisms generate HLA class I altered phenotypes in laryngeal carcinomas: high frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21

Cancer Immunology Immunotherapy ◽

10.1007/s00262-002-0296-0 ◽

2002 ◽

Vol 51 (7) ◽

pp. 389-396 ◽

Cited By ~ 64

Author(s):

Isabel Maleno ◽

Miguel López-Nevot ◽

Teresa Cabrera ◽

José Salinero ◽

Federico Garrido

Keyword(s):

Loss Of Heterozygosity ◽

High Frequency ◽

Chromosome Region ◽

Hla Class I ◽

Class I ◽

Laryngeal Carcinomas

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Genetically Determined Strength of Natural Killer Cells is Enhanced by Adaptive HLA class I Admixture in East Asians

10.1101/2020.07.29.227579 ◽

2020 ◽

Author(s):

Zhihui Deng ◽

Jianxin Zhen ◽

Genelle F. Harrison ◽

Guobin Zhang ◽

Rui Chen ◽

...

Keyword(s):

Natural Selection ◽

Natural Killer ◽

High Frequency ◽

Nk Cell ◽

Hla Class I ◽

Class I ◽

Telomeric Region ◽

East Asians ◽

Cell Functions ◽

Specific Receptors

AbstractHuman natural killer (NK) cells are essential for controlling infection, cancer and fetal development. NK cell functions are modulated by interactions between polymorphic inhibitory killer cell immunoglobulin-like receptors (KIR) and polymorphic HLA-A, -B and -C ligands expressed on tissue cells. All HLA-C alleles encode a KIR ligand and contribute to reproduction and immunity. In contrast, only some HLA-A and -B alleles encode KIR ligands and they focus on immunity. By high-resolution analysis of KIR and HLA-A, -B and -C genes, we show that the Chinese Southern Han are significantly enriched for interactions between inhibitory KIR and HLA-A and -B. This enrichment has had substantial input through population admixture with neighboring populations, who contributed HLA class I haplotypes expressing the KIR ligands B*46:01 and B*58:01, which subsequently rose to high frequency by natural selection. Consequently, over 80% of Southern Han HLA haplotypes encode more than one KIR ligand. Complementing the high number of KIR ligands, the Chinese Southern Han KIR locus combines a high frequency of genes expressing potent inhibitory KIR, with a low frequency of those expressing activating KIR. The Southern Han centromeric KIR region encodes strong, conserved, inhibitory HLA-C specific receptors, and the telomeric region provides a high number and diversity of inhibitory HLA-A and -B specific receptors. In all these characteristics, the Southern Han represent other East Asians, whose NK cell repertoires are thus enhanced in quantity, diversity and effector strength, likely through natural selection for resistance to endemic viral infections.

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An estimate of heterosis in Drosophila melanogaster

Genetics Research ◽

10.1017/s0016672300012453 ◽

1971 ◽

Vol 18 (1) ◽

pp. 97-105 ◽

Cited By ~ 54

Author(s):

J. A. Sved

Keyword(s):

Drosophila Melanogaster ◽

High Frequency ◽

Marker Chromosome ◽

Selective Advantage ◽

Wild Type ◽

Set Up

SUMMARYTwenty-five population cages of D. melanogaster were set up, each containing a different wild-type second chromosome and the marker chromosome Cy. In all but one case where contamination apparently occurred, the Cy chromosome persisted in the population at high frequency, showing a selective advantage of Cy/ + heterozygotes over wild-type homozygotes. Overall, the results indicate that homozygosity of the entire second chromosome causes a depression in fitness of the order of 85%.

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Do African and European ancestry and polymorphism of HLA class I play an important role in controlling HTLV-1 proviral load in admixed cohorts from Salvador, Brazil?

Retrovirology ◽

10.1186/1742-4690-11-s1-p76 ◽

2014 ◽

Vol 11 (S1) ◽

Cited By ~ 1

Author(s):

Viviana Nilla Olavarria ◽

Eduardo José Melo dos Santos ◽

Sidney Emanuel Batista dos Santos ◽

Fernanda Grassi ◽

Ramon Kruchewesky ◽

...

Keyword(s):

Proviral Load ◽

Hla Class I ◽

Class I ◽

European Ancestry

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Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well-documented population from sub-Saharan Africa

HLA ◽

10.1111/tan.13180 ◽

2017 ◽

Vol 91 (1) ◽

pp. 36-51 ◽

Cited By ~ 10

Author(s):

T. Goeury ◽

L. E. Creary ◽

L. Brunet ◽

M. Galan ◽

M. Pasquier ◽

...

Keyword(s):

Nucleotide Diversity ◽

Hla Class I ◽

Class Ii ◽

Sub Saharan Africa ◽

Class I ◽

Sub Saharan

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High frequency of alternative first exons in erythroid genes suggests a critical role in regulating gene function

Blood ◽

10.1182/blood-2005-07-2957 ◽

2006 ◽

Vol 107 (6) ◽

pp. 2557-2561 ◽

Cited By ~ 24

Author(s):

Jeff S. Tan ◽

Narla Mohandas ◽

John G. Conboy

Keyword(s):

Human Genome ◽

High Frequency ◽

Critical Role ◽

Test Group ◽

Protein Isoforms ◽

Alternative Promoters ◽

Transcriptional Promoters ◽

Show Evidence ◽

Computational Analyses ◽

Frequent Presence

AbstractThe human genome uses alternative pre-mRNA splicing as an important mechanism to encode a complex proteome from a relatively small number of genes. An unknown number of these genes also possess multiple transcriptional promoters and alternative first exons that contribute another layer of complexity to gene expression mechanisms. Using a collection of more than 100 erythroid-expressed genes as a test group, we used genome browser tools and genetic databases to assess the frequency of alternative first exons in the genome. Remarkably, 35% of these erythroid genes show evidence of alternative first exons. The majority of the candidate first exons are situated upstream of the coding exons, whereas a few are located internally within the gene. Computational analyses predict transcriptional promoters closely associated with many of the candidate first exons, supporting their authenticity. Importantly, the frequent presence of consensus translation initiation sites among the alternative first exons suggests that many proteins have alternative N-terminal structures whose expression can be coupled to promoter choice. These findings indicate that alternative promoters and first exons are more widespread in the human genome than previously appreciated and that they may play a major role in regulating expression of selected protein isoforms in a tissue-specific manner. (Blood. 2006;107: 2557-2561)

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