共查询到20条相似文献,搜索用时 15 毫秒
1.
The killer cell immunoglobulin-like receptor (KIR) gene cluster exhibits extensive allelic and haplotypic diversity. Variation
at the locus is associated with an increasing number of human diseases, reminiscent of the HLA loci. Characterization of diversity at the KIR locus has progressed over the past several years, particularly since the sequence of entire KIR haplotypes have become available. To determine the extent of KIR haplotypic variability among individuals of northern European descent, we genotyped 59 CEPH families for presence/absence
of all KIR genes and performed limited allelic subtyping at several KIR loci. A total of 20 unique haplotypes differing in gene content were identified, the most common of which was the previously
defined A haplotype (f = 0.52). Several unusual haplotypes that probably arose as a consequence of unequal crossing over events
were also identified. Linkage disequilibrium (LD) analysis indicated strong negative and positive LD between several pairs
of genes, values that may be useful in determining haplotypic structure when family data are not available. These data provide
a resource to aid in the interpretation of disease association data involving individuals of European descent.
An erratum to this article can be found at 相似文献
2.
Certain combinations of the killer immunoglobulin-like receptors (KIR) and major histocompatibility complex class I ligands
in humans predispose carriers to a variety of diseases, requiring sophisticated genotyping of the highly polymorphic and diverse
KIR and HLA genes. Particularly, KIR genotyping is challenging due to polymorphisms (allelic substitutions), genomic diversity (presence/absence of genes), and
frequent duplications. Rhesus macaques are often used as important animal models of human diseases such as, e.g. AIDS. However,
typing of rhesus macaque KIR genes has not been described so far. In this study, we report the identification of additional novel rhesus macaque KIR cDNA sequences and a sequence-specific KIR genotyping assay. From a cohort of four rhesus macaque families with a total of 70 individuals, we identified 25 distinct
KIR genotypes. Segregation analyses of KIR genes and of two polymorphic microsatellite markers allowed the identification of 21 distinct KIR haplotypes in these families, with five to 11 segregating KIR genes per haplotype. Our analyses confirmed and extended knowledge on differential gene KIR gene content in macaques and indicate that rhesus macaque and human KIR haplotypes show a comparable level of diversity and complexity. 相似文献
3.
Laurent Vidard Thierry Roger Ghislaine Pham Jacques Couderc Yolande Bouthillier Jean-Claude Mevel Denise Mouton Michel Seman 《Immunogenetics》1990,32(1):27-33
Tcrb andTcrg gene polymorphism was investigated in high (H) and low (L) responder Biozzi mice from selection I, II, and GS by Southern blot analysis with appropriateV andC probes. No polymorphism of theTcrb haplotype was detected between H and L mice in all selections which were all found to be of the BALB/c type. The H-I and H-II g genotype was of BALB/c and DBA/2 type, respectively. In contrast, a newTcrg haplotype shared by L-I and L-II mice was identified and characterized by C1, 2, 3, C4, V1, 2, 3, V5, and V6 restriction fragment length polymorphisms (RFLPs).Tcrg genotypes were not fixed in the GS selection and two additional new haplotypes were identified in two L-GS mice. An attempt was made to correlate the L-Ig genotype with the low responder status by analyzingg haplotypes among highest and lowest responder (H-1 x L-I)F2 hybrids immunized with sheep red blood cells (SRBC). No correlation was found in this segregation study, whereas a highly significant one was established with theH-2 haplotype, a locus already known to participate in the genetic control of H-I/L-I difference. The lack of correlation between SRBC response and theTcrg genotype was consistent with the heterogenousg haplotypes found in mice of the GS selection. Together, the present results suggest that H and L mice have the sameTcrab potential repertoire and that T-cell receptor (Tcr) genes cannot be considered as immune response genes in this model. Our results also indicate that the F2 segregation analysis, given a polymorphic gene, is suitable for an investigation of its immune response functions. 相似文献
4.
Methods for assessing gene content diversity of KIR with examples from a global set of populations 总被引:1,自引:1,他引:0
A number of statistical methods are widely used to describe allelic variation at specific genetic loci and its implication
on the evolutionary history of these loci. Although the methods were developed primarily to study allelic variation at loci
that are virtually always present in the genome, they are often applied to data of gene content variation (i.e., presence/absence
of multiple homologous genes) at the killer cell immunoglobulin-like receptor (KIR) gene cluster. In this paper, we discuss methodological issues involved in the analysis of gene content variation data in
the KIR region and also its covariation with polymorphism at the human leukocyte antigen class I loci, which encode ligands
for KIR. A comparison of several statistical methods and measures (gene frequency, haplotype frequency, and linkage disequilibrium
estimation) using the Centre d’Etude du Polymorphisme Humain data will be provided using KIR haplotypes that have been determined
by segregation analysis, noting the strengths and weaknesses of the methods when only the presence/absence data is considered.
Finally, application of these methods to a set of globally distributed populations is described (see Single et al., Nat Genet
39:1114–1119, 2007) in order to illustrate the challenges faced when inferring the joint effects of natural selection and demographic history
on these immune-related genes. 相似文献
5.
Rajalingam R Du Z Meenagh A Luo L Kavitha VJ Pavithra-Arulvani R Vidhyalakshmi A Sharma SK Balazs I Reed EF Pitchappan RM Middleton D 《Immunogenetics》2008,60(5):207-217
By interacting with polymorphic HLA class I molecules, the killer cell immunoglobulin-like receptors (KIR) influence the innate
and adaptive immune response to infection. The KIR family varies in gene content and sequence polymorphism, thereby, distinguishing individuals and populations. To investigate
KIR diversity in the earliest settlers of India, we have characterized the KIR gene content in three Dravidian-speaking populations (Mollukurumba, Kanikar, and Paravar) from the state of Tamil Nadu, southern
India. The activating KIR genes and putative group-B KIR haplotypes were frequent in Paravar and Kanikar, a scenario analogous to those seen previously in other populations of Indian
origin, indicating that predominance of group-B KIR haplotypes is the characteristic feature of Indian populations. In contrast, the KIR gene profile of Mollukurumba was more related to Caucasian type. It is not clear whether a local-specific selection or a
recent admixture from Iran is responsible for such discrete profile in Mollukurumba. Each southern Indian population had distinct
KIR genotype profile. Comparative analyses with world populations revealed that group-B KIR haplotypes were frequent in the natives of India, Australia, and America, the populations associated with those involved
in extensive prehistoric human migrations. Whether or not natural selection has acted to enrich group-B KIR haplotypes in these migratory descendants is an issue that requires objective testing.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
6.
Susan E. Hiby Maziar Ashrafian-Bonab Lydia Farrell Richard M. Single Francois Balloux Mary Carrington Ashley Moffett 《Immunogenetics》2010,62(2):65-73
Killer cell immunoglobulin-like receptors (KIR) gene frequencies vary between populations and contribute to functional variation in immune responses to viruses, autoimmunity
and reproductive success. This study describes the frequency distribution of 12 variable KIR genes and their HLA-C ligands in two Iranian populations who have lived for many generations in different environments: the
Azerbaijanis at high altitude and the Jonobi people at sea level. The results are compared with those published for other
human populations and a large group of English Caucasians. Differences were seen in KIR and HLA-C group frequencies, in linkage disequilibrium and inhibitory/activating KIR ratios between the groups. Similarities with geographically close populations in the frequencies of the KIR A and B haplotypes and KIR AA genotype reflected their common ancestry. The extreme variability of the KIR gene family and their HLA-C ligands is highlighted and their importance in defining differences between geographically and
culturally isolated communities subject to different environmental pressures who come from the same ethnic grouping. 相似文献
7.
Jennes W Verheyden S Demanet C Menten J Vuylsteke B Nkengasong JN Kestens L 《PloS one》2011,6(2):e17043
Natural killer (NK) cells are regulated by interactions between polymorphic
killer immunoglobulin-like receptors (KIR) and human leukocyte antigens (HLA).
Genotypic combinations of KIR3DS1/L1 and HLA
Bw4-80I were previously shown to influence HIV-1 disease
progression, however other KIR genes have not been well
studied. In this study, we analyzed the influence of all activating and
inhibitory KIR, in association with the known HLA inhibitory KIR ligands, on
markers of disease progression in a West African population of
therapy-naïve HIV-1 infected subjects. We observed a significant
association between carriage of a group B KIR haplotype and
lower CD4+ T cell counts, with an additional effect for
KIR3DS1 within the frame of this haplotype. In contrast, we
found that individuals carrying genes for the inhibitory KIR ligands
HLA-Bw4 as well as HLA-C1 showed
significantly higher CD4+ T cell counts. These associations were
independent from the viral load and from individual HIV-1 protective HLA
alleles. Our data suggest that group B KIR haplotypes and lack
of specific inhibitory KIR ligand genes, genotypes considered to favor NK cell
activation, are predictive of HIV-1 disease progression. 相似文献
8.
Killer cell immunoglobulin-like receptor (KIR) genes and their HLA-C ligands in a Ugandan population
Annettee Nakimuli Olympe Chazara Lydia Farrell Susan E. Hiby Stephen Tukwasibwe Olatejumoye Knee Jyothi Jayaraman James A. Traherne Alison M. Elliott Pontiano Kaleebu Florence Mirembe Ashley Moffett 《Immunogenetics》2013,65(11):765-775
Killer cell immunoglobulin-like receptor (KIR) genes are expressed by natural killer cells and encoded by a family of genes exhibiting considerable haplotypic and allelic variation. HLA-C molecules, the dominant ligands for KIR, are present in all individuals and are discriminated by two KIR epitopes, C1 and C2. We studied the frequencies of KIR genes and HLA-C1 and C2 groups in a large cohort (n?=?492) from Kampala, Uganda, East Africa and compared our findings with published data from other populations in sub-Saharan Africa (SSA) and several European populations. We find considerably more KIR diversity and weaker linkage disequilibrium in SSA compared to the European populations and describe several novel KIR genotypes. C1 and C2 frequencies were similar to other SSA populations with a higher frequency of the C2 epitope (54.9 %) compared to Europe (average 39.7 %). Analysis of this large cohort from Uganda in the context of other African populations reveals variations in KIR and HLA-C1 and C2 that are consistent with migrations within Africa and potential selection pressures on these genes. Our results will help understand how KIR/HLA-C interactions contribute to resistance to pathogens and reproductive success. 相似文献
9.
Killer cell immunoglobulin-like receptors (KIR) gene frequencies have been shown to be distinctly different between populations and contribute to functional variation in
the immune response. We have investigated KIR gene frequencies in 370 individuals representing three Asian populations in Singapore and report here the distribution of
14 KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) with two pseudogenes (2DP1, 3DP1) among Singapore Chinese (n = 210); Singapore Malay (n = 80), and Singapore Indian (n = 80). Four framework genes (KIR3DL3, 3DP1, 2DL4, 3DL2) and a nonframework pseudogene 2DP1 were detected in all samples while KIR2DS2, 2DL2, 2DL5, and 2DS5 had the greatest significant variation across the three populations. Fifteen significant linkage patterns, consistent with
associations between genes of A and B haplotypes, were observed. Eighty-four distinct KIR profiles were determined in our populations, 38 of which had not been described in other populations. KIR haplotype studies
were performed using nine Singapore Chinese families comprising 34 individuals. All genotypes could be resolved into corresponding
pairs of existing haplotypes with eight distinct KIR genotypes and eight different haplotypes. The haplotype A2 with frequency of 63.9% was dominant in Singapore Chinese, comparable to that reported in Korean and Chinese Han. The A haplotypes predominate in Singapore Chinese, with ratio of A to B haplotypes of approximately 3:1. Comparison with KIR frequencies in other populations showed that Singapore Chinese shared similar distributions with Chinese Han, Japanese, and
Korean; Singapore Indian was found to be comparable with North Indian Hindus while Singapore Malay resembled the Thai.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
10.
A migration with admixture of genes in two populations inducesHL-A linkage disequilibrium or when gene frequencies in the two populations are dissimilar. Since theHL-A linkage disequilibrium disappears very slowly, this factor could be used to recognize some migrations. In the recent migration of American Negroes, a dilution of Caucasoid disequilibrium is noted. By the presence of values, a study of possible migrations around the world is reported and a brief comparison with other methods of research into population origins is discussed in connection with the European ecosphere: a well-known expansion axis is found from East to West (probably due to the Indo-European migration), which ends with admixture with various local Western European populations. Another expansion of genes is noted from the North of Europe towards the Southwest. 相似文献
11.
Neda Nemat-Gorgani Hisham A. Edinur Jill A. Hollenbach James A. Traherne Paul P. J. Dunn Geoffrey K. Chambers Peter Parham Paul J. Norman 《Immunogenetics》2014,66(11):597-611
HLA class I molecules and killer cell immunoglobulin-like receptors (KIR) form a diverse system of ligands and receptors that individualize human immune systems in ways that improve the survival of individuals and populations. Human settlement of Oceania by island-hopping East and Southeast Asian migrants started ~3,500 years ago. Subsequently, New Zealand was reached ~750 years ago by ancestral Māori. To examine how this history impacted KIR and HLA diversity, and their functional interaction, we defined at high resolution the allelic and haplotype diversity of the 13 expressed KIR genes in 49 Māori and 34 Polynesians. Eighty KIR variants, including four ‘new’ alleles, were defined, as were 35 centromeric and 22 telomeric KIR region haplotypes, which combine to give >50 full-length KIR haplotypes. Two new and divergent variant KIR form part of a telomeric KIR haplotype, which appears derived from Papua New Guinea and was probably obtained by the Asian migrants en route to Polynesia. Māori and Polynesian KIR are very similar, but differ significantly from African, European, Japanese, and Amerindian KIR. Māori and Polynesians have high KIR haplotype diversity with corresponding allotype diversity being maintained throughout the KIR locus. Within the population, each individual has a unique combination of HLA class I and KIR. Characterizing Māori and Polynesians is a paucity of HLA-B allotypes recognized by KIR. Compensating for this deficiency are high frequencies (>50 %) of HLA-A allotypes recognized by KIR. These HLA-A allotypes are ones that modern humans likely acquired from archaic humans at a much earlier time. 相似文献
12.
Damjan Vukcevic James?A. Traherne Sigrid N?ss Eva Ellinghaus Yoichiro Kamatani Alexander Dilthey Mark Lathrop Tom?H. Karlsen Andre Franke Miriam Moffatt William Cookson John Trowsdale Gil McVean Stephen Sawcer Stephen Leslie 《American journal of human genetics》2015,97(4):593-607
Large population studies of immune system genes are essential for characterizing their role in diseases, including autoimmune conditions. Of key interest are a group of genes encoding the killer cell immunoglobulin-like receptors (KIRs), which have known and hypothesized roles in autoimmune diseases, resistance to viruses, reproductive conditions, and cancer. These genes are highly polymorphic, which makes typing expensive and time consuming. Consequently, despite their importance, KIRs have been little studied in large cohorts. Statistical imputation methods developed for other complex loci (e.g., human leukocyte antigen [HLA]) on the basis of SNP data provide an inexpensive high-throughput alternative to direct laboratory typing of these loci and have enabled important findings and insights for many diseases. We present KIR∗IMP, a method for imputation of KIR copy number. We show that KIR∗IMP is highly accurate and thus allows the study of KIRs in large cohorts and enables detailed investigation of the role of KIRs in human disease. 相似文献
13.
Diversity of killer cell immunoglobulin-like receptor genes in Pacific Islands populations 总被引:10,自引:7,他引:3
Killer immunoglobulin-like receptors (KIRs) regulate the activity of NK and T cells through interaction with specific HLA class I molecules on target cells. To date, 16 KIR genes and pseudogenes have been identified. Diversity in KIR gene content and KIR allelic and haplotype polymorphism has been observed between different ethnic groups. Here, we present data on the KIR gene distribution in Pacific Islands populations. Sixteen KIR genes were observed in Pacific Islands populations from the Cook Islands, Samoa, Tokelau, and Tonga. The majority of KIR genes were present at similar frequencies between the four populations with KIR2DL4, KIR3DL2, and KIR3DP1 genes observed in all individuals. Commonly observed KIR genes in Pacific Islands populations (pooled frequencies) were KIR2DL1 (0.77), KIR2DL3 (0.77), KIR3DL1 (0.65), KIR3DL3 (0.93), KIR2DS4/1D (0.78), and KIR2DP1 (0.82), compared to the less-frequently observed KIR2DL2 (0.27), KIR2DL5 (0.30), KIR2DS1 (0.19), KIR2DS2 (0.27), KIR2DS3 (0.16), KIR2DS5 (0.17), and KIR3DS1 (0.18) genes. Differences in KIR gene frequency distributions were observed between the Pacific Islands populations and when compared to other populations. Sixty-nine different genotypes were identified, with five genotypes accounting for more then 50% of all genotypes observed. The number of genotypes observed in each population was similar in the Cook Islands, Samoan, and Tokelauan populations (19, 18, and 19, respectively), but 26 different genotypes were observed in Tongans. The putative haplotype A was predominantly observed over haplotype B in all Pacific Islands populations. Significant linkage disequilibrium was observed for a number of KIR gene pairs. 相似文献
14.
Interaction between killer cell immunoglobulin-like receptors (KIR) and cognate HLA class I ligands influences the innate and adaptive immune response to infection. The KIR family varies in gene content and allelic polymorphism, thereby, distinguishing individuals and populations. KIR gene content was determined for 230 individuals from three Amerindian tribes from Venezuela: the Yucpa, Bari and Warao. Gene-content haplotypes could be assigned to 212 individuals (92%) because only five different haplotypes were present—group A and four group B. Six different haplotype combinations accounted for >80% of individuals. Each tribe has distinctive genotype frequencies. Despite few haplotypes, all 14 KIR genes are at high frequency in the three tribes, with the exception of 2DS3. Each population has an even frequency of group A and B haplotypes. Allele-level analysis of 3DL1/S1 distinguished five group A haplotypes and six group B haplotypes. The high frequency and divergence of the KIR haplotypes in the Amerindian tribes provide greater KIR diversity than is present in many larger populations. An extreme case being the Yucpa, for whom two gene-content haplotypes account for >90% of the population. These comprise the group A haplotype and a group B haplotype containing all the KIR genes, except 2DS3, that typify the group B haplotypes. Here is clear evidence for balancing selection on the KIR system and the biological importance of both A and B haplotypes for the survival of human populations.Electronic Supplementary Material Supplementary material is available for this article at 相似文献
15.
The genomic organization and evolution of the natural killer immunoglobulin-like receptor (KIR) gene cluster 总被引:18,自引:7,他引:11
Natural killer (NK) immunoglobulin-like receptors (KIRs) are a family of polymorphic receptors which interact with specific
motifs on HLA class I molecules and modulate NK cytolytic activity. In this study, we analyzed a recently sequenced subgenomic
region on chromosome 19q13.4 containing eight members of the KIR receptor repertoire. Six members are clustered within a 100-kb continuous sequence. These genes include a previously unpublished
member of the KIR gene family 2DS6, as well as 2DL1, 2DL4, 3DL1, 2DS4, 3DL2, from centromere to telomere. Two additional KIR genes, KIRCI and 2DL3, which may be located centromeric of this cluster were also analyzed. We show that the KIR genes have undergone repeated gene duplications. Diversification between the genes has occurred postduplication primarily
as a result of retroelement indels and gene truncation. Using pre- and postduplication Alu sequences identified within these
genes as evolutionary molecular clocks, the evolution and duplication of this gene cluster is estimated to have occurred 30–45 million
years ago, during primate evolution. A proposed model of the duplication history of the KIR gene family leading to their present organization is presented.
Received: 25 November 1999 / Revised: 10 January 2000 相似文献
16.
Augusto DG Zehnder-Alves L Pincerati MR Martin MP Carrington M Petzl-Erler ML 《Immunogenetics》2012,64(2):143-152
The activity of natural killer cells depends on the balance between activating and inhibitory signals coming from their receptors.
Among these are the killer cell immunoglobulin-like receptors (KIR) that recognize specific HLA class I allotypes. Here we
characterized KIR genetic diversity and their HLA ligands in the population of Curitiba, Paraná State (n = 164), and compared it with other worldwide populations. The distribution of 2DL4 alleles was also analyzed. The Curitiba population did not differ significantly from European and Euro-descendant populations,
but as an admixed population showed higher genetic diversity. We found 27 KIR profiles, many of them uncommon in European populations, in agreement with the elevated historically recent gene flow in
the study population. The frequencies of KIR genes and their respective HLA ligands were distributed independently and none of the analyzed individuals lacked functional
KIR–HLA ligand combinations. KIR gene frequencies of 33 worldwide populations were consistent with geographic and ethnic distribution, in agreement with demography
being the major factor shaping the observed gene content diversity of the KIR locus. 相似文献
17.
Luciana de Brito Vargas Marcia H Beltrame Brenda Ho Wesley M Marin Ravi Dandekar Gonzalo Montero-Martín Marcelo A Fernndez-Via A Magdalena Hurtado Kim R Hill Luiza T Tsuneto Mara H Hutz Francisco M Salzano Maria Luiza Petzl-Erler Jill A Hollenbach Danillo G Augusto 《Molecular biology and evolution》2022,39(1)
The killer-cell immunoglobulin-like receptors (KIR) recognize human leukocyte antigen (HLA) molecules to regulate the cytotoxic and inflammatory responses of natural killer cells. KIR genes are encoded by a rapidly evolving gene family on chromosome 19 and present an unusual variation of presence and absence of genes and high allelic diversity. Although many studies have associated KIR polymorphism with susceptibility to several diseases over the last decades, the high-resolution allele-level haplotypes have only recently started to be described in populations. Here, we use a highly innovative custom next-generation sequencing method that provides a state-of-art characterization of KIR and HLA diversity in 706 individuals from eight unique South American populations: five Amerindian populations from Brazil (three Guarani and two Kaingang); one Amerindian population from Paraguay (Aché); and two urban populations from Southern Brazil (European and Japanese descendants from Curitiba). For the first time, we describe complete high-resolution KIR haplotypes in South American populations, exploring copy number, linkage disequilibrium, and KIR–HLA interactions. We show that all Amerindians analyzed to date exhibit the lowest numbers of KIR–HLA interactions among all described worldwide populations, and that 83–97% of their KIR–HLA interactions rely on a few HLA-C molecules. Using multiple approaches, we found signatures of strong purifying selection on the KIR centromeric region, which codes for the strongest NK cell educator receptors, possibly driven by the limited HLA diversity in these populations. Our study expands the current knowledge of KIR genetic diversity in populations to understand KIR–HLA coevolution and its impact on human health and survival. 相似文献
18.
p53 polymorphisms in Russia and Belarus: correlation of the 2-1-1 haplotype frequency with longitude
Khrunin AV Tarskaia LA Spitsyn VA Lylova OI Bebyakova NA Mikulich AI Limborska SA 《Molecular genetics and genomics : MGG》2005,272(6):666-672
Four different polymorphisms in the human p53 gene (a 16-bp duplication in intron 3, and three RFLPs: for Bsh1236I at codon 72, for MspI in intron 6 and for BamHI in the 3 flanking region) and extended haplotypes were studied in nine geographically diverse populations from Russia and Belarus. The Yakuts differed from all other populations, as they had a significantly higher frequency of the BamHI A1 allele. Most populations did not differ significantly from each other in the frequency of the Bsh1236I polymorphism. The 16-bp duplication A1 allele and MspI A2 allele frequencies were significantly higher in the Yakut and Khant populations. Linkage disequilibrium values (D) between BamHI and other polymorphic sites were not significant in many cases; for this reason we have used the 16 bp–Bsh1236I–MspI haplotype frequencies only. Of eight possible haplotypes, five were observed in the populations investigated. Haplotype 1-2-2 was the most frequent in all populations. The next most common haplotype, 1-1-2, was present at very similar frequencies among the Byelorussians and Russians from Smolensk, but was more frequent in other populations. The frequency of haplotype 2-1-1 showed a nearly continuous decrease from West to East (from 17.857% among the Byelorussians to 0.685% in the Yakuts from the Verkhoyansk) and correlated with longitude (Spearmans r=–0.8667, P=0.0025), which may be due to natural selection and adaptation. The relationships among populations were evaluated by means of Neis DA distances for the 16 bp–Bsh1236I–MspI haplotype frequencies. Based on the multidimensional scaling analysis a correlation between p53 haplotype frequencies and ethnicity is supposed. 相似文献
19.
Heidinger K König IR Bohnert A Kleinsteiber A Hilgendorff A Gortner L Ziegler A Chakraborty T Bein G 《Immunogenetics》2005,57(1-2):1-7
The collectin surfactant protein-D (SP-D) plays a significant role in innate immunity. Epidemiological studies described associations between single nucleotide polymorphisms (SNPs) of the human gene coding surfactant protein-D (SFTPD) and infectious pulmonary diseases. Studies on twins indicated very strong genetic dependence for serum levels of SP-D. The aim of this study was to determine the genetic influence of sequence variations within the SFTPD gene on the constitutional serum SP-D levels. We sequenced the 5 untranslated region (5UTR), the coding region and the 3 region of the SFTPD gene of 32 randomly selected blood donors. Six validated SNPs were genotyped with sequence-specific probes (TaqMan 7000) in 290 German blood donors. Serum SP-D levels were analysed by ELISA, and the association of SFTPD haplotype estimates with the quantitative phenotype serum SP-D level was determined. One single SFTPD haplotype (allele frequency 13.53%) revealed a negative association with serum SP-D levels (P<0.0001). This was confirmed in a second prospectively collected group of blood donors (n=160, P=0.0034). The discovery of a frequent negative variant of the SFTPD gene provides a basis for genetic analysis of the function of SP-D in the resistance against pulmonary infections and inflammatory disorders in humans. 相似文献
20.
A single-base deletion in soybean flavonoid 3′-hydroxylase gene is associated with gray pubescence color 总被引:5,自引:0,他引:5
Toda K Yang D Yamanaka N Watanabe S Harada K Takahashi R 《Plant molecular biology》2002,50(2):187-196
The T locus of soybean (Glycine max (L.) Merr.) controls pubescence and seed coat color and is presumed to encode flavonoid 3-hydroxylase (F3H). The dominant T and the recessive t allele of the locus produce brown and gray pubescence, respectively. PCR primers were constructed based on the sequence of a soybean EST clone homologous to the F3H gene. A putative full-length cDNA, sf3h1 was isolated by 3 and 5 RACE. Sequence analysis revealed that sf3h1 consists of 1690 nucleotides encoding 513 amino acids. It had 68% and 66% homology with corresponding F3H protein sequences of petunia and Arabidopsis, respectively. A conserved amino acid sequence of F3H proteins, GGEK, was found in the deduced polypeptide. Sequence analysis of the gene from a pair of near-isogenic lines for T, To7B (TT, brown) and To7G (tt, gray) revealed that they differed by a single C deletion in the coding region of To7G. The deletion changed the subsequent reading frame resulting in a truncated polypeptide lacking the GGEK consensus sequence and the heme-binding domain. Genomic Southern analysis probed by sf3h1 revealed restriction fragment length polymorphisms between cultivars with different pubescence color. Further, sf3h1 was mapped at the same position with T locus on LG3(c2). PCR-RFLP analysis was performed to detect the single-base deletion. To7B and three cultivars with brown pubescence exhibited shorter fragments, while To7G and three cultivars with gray pubescence had longer fragments due to the single-base deletion. The PCR-RFLP marker co-segregated with genotypes at the Tlocus in a F2 population segregating for the T locus. The above results strongly suggest that sf3h1 represents the T gene of soybean responsible for pubescence color and that the single-base deletion may be responsible for gray pubescence color. 相似文献