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1.
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 These genes include a previously unpublished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
2.
SNP haplotypes and allele frequencies show evidence for disruptive and balancing selection in the human leukocyte receptor complex 总被引:4,自引:3,他引:1
Norman PJ Cook MA Carey BS Carrington CV Verity DH Hameed K Ramdath DD Chandanayingyong D Leppert M Stephens HA Vaughan RW 《Immunogenetics》2004,56(4):225-237
The human leukocyte receptor complex (LRC) of Chromosome 19q13.4 encodes polymorphic and highly homologous genes that are expressed by cells of the immune system and regulate their function. There is an enormous diversity at the LRC, most particularly the variable number of killer cell immunoglobulin-like receptor (KIR) genes. KIR have been associated with several disease processes due to their interaction with polymorphic human leukocyte antigen class I molecules. We have assessed haplotype compositions, linkage disequilibrium patterns and allele frequencies in two Caucasoid population samples (n=54, n=100), using a composite of single-nucleotide polymorphism (SNP) markers and high-resolution, allele-specific molecular genotyping. Particular KIR loci segregated with SNP and other markers, forming two blocks that were separated by a region with a greater history of recombination. The KIR haplotype composition and allele frequency distributions were consistent with KIR having been subject to balancing selection (Wattersons F: P=0.001). In contrast, there was a high inter-population heterogeneity measure for the LRC-encoded leukocyte immunoglobulin-like receptor A3 (LILRA3), indicating pathogen-driven disruptive selection (Wrights FST=0.32). An assessment of seven populations representative of African, Asian and Caucasoid ethnic groups (total n=593) provided little evidence for long-range LRC haplotypes. The different natural selection pressures acting on each locus may have contributed to a lack of linkage disequilibrium between them. 相似文献
3.
We analyzed two-locus disequilibria for 16 polymorphic loci of seven susceptibility genes for coronary artery disease located
in five chromosomal regions distributed across four chromosomes. Included were the genes coding for apolipoprotein B (ApoB, chromosome 2, four marker loci), lipoprotein lipase (LPL, chromosome 8, three marker loci), apolipoproteins AI, CIII, AIV (ApoAI–CIII–AIV, chromosome 11, three marker loci), apolipoprotein E (ApoE, chromosome 19, two marker loci), and the low density lipoprotein receptor (LDLR, chromosome 19, four marker loci). Our sample included 540 unrelated individuals from the Rochester, Minn. population. There
were no statistically significant deviations of single-locus genotypes from Hardy-Weinberg equilibrium. The strongest associations
within genes were for composite diallelic disequilibria; 17/19 were significant (13 at Pr <0.001, 1 at Pr <0.01, 3 at Pr <0.05). These observations suggest marker alleles within genes have a shared evolutionary history reflected by disequilibria
that have not been dissipated by recombination. Disequilibrium was not generally concordant with the physical orderings of
markers. Only two significant higher-order disequilibria were observed although 12 triallelic disequilibria were at maximum
possible values. We observed 19 statistically significant disequilibria (Pr <0.05; 4 composite diallelic, 13 triallelic, and 2 quadriallelic) between 101 pairs of marker loci, where each locus in a
pair was from a different unlinked region. These unexpected results are most likely explained by recent historical factors,
including worldwide population expansion and amalgamation with continuous admixture, that influence the genetic structure
(organization of alleles and non-alleles into genotypes) of a population. We conclude that disequilibria between loci from
unlinked regions may be more extensive than is commonly assumed. Our findings also suggest that it is, on average, at least
15 times more likely to not detect significant disequilibrium among unlinked loci when it is really present than to make a
false positive inference. Disequilibria between functional loci within or between regions will impact estimates of genetic
variance associated with particular functional mutations within a susceptibility gene region.
Received: 15 January 1998 / Accepted: 24 June 1998 相似文献
4.
5.
D. E. Koryakov A. A. Alekseyenko I. F. Zhimulev 《Molecular & general genetics : MGG》1999,260(6):503-509
Region 20 of the polytene X chromosome of Drosophila melanogaster was studied in salivary glands (SG) and pseudonurse cells (PNC) of otu mutants. In SG chromosomes the morphology of the region strongly depends on two modifiers of position effect variegation:
temperature and amount of heterochromatin. It is banded in XYY males at 25° C and β-heterochromatic in X0 males at 14° C, i.e. it shows dynamic transitions. In PNC chromosomes region 20 is not heterochromatic, but demonstrates
a clear banding pattern. Some molecular markers of mitotic heterochromatin were localized by means of in situ hybridization
on PNC chromosomes: DNA of the gene su(f) in section 20C, the nucleolar organizer and 359-bp satellite in 20F. The 359-bp satellite, which has been considered to be
specific for heterochromatin of the mitotic X chromosome, was found at two additional sites on chromosome 3L, proximally to 80C. The right arm of the X chromosome in SG chromosomes was localized in the inversion In(1LR)pn2b: the telomeric HeT-A DNA and AAGAG satellite from the right arm are polytenized, having been relocated from heterochromatin to euchromatin.
Received: 1 July 1998 / Accepted: 7 September 1998 相似文献
6.
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
7.
Ly49 genes regulate the cytotoxic activity of natural killer (NK) cells in rodents and provide important protection against virus-infected or tumor cells. About 15 Ly49 genes have been identified in mice, but only a few genes have been reported to date in rats. Here we studied all Ly49 genes in the entire rat genome sequence and identified 17 putative functional and 16 putative non-functional genes together with their genomic locations in a 1.8-Mb region of chromosome 4. Phylogenetic analysis of these genes indicated that the Ly49 gene family expanded rapidly in recent years, and this expansion was mediated by both tandem and genomic block duplication. The joint phylogenetic analysis of mouse and rat genes suggested that the most recent common ancestor of the two species had at least several Ly49 genes, but that the majority of current duplicate genes were generated after divergence of the two species. In both species Ly49 genes are apparently subject to birth-and-death evolution, but the birth and death rates of Ly49 genes are higher in rats than in mice. The rate of gene expansion in the Ly49 gene family in rats is one of the highest among all mammalian multigene families so far studied. The biochemical function of Ly49 genes is essentially the same as that of KIR genes in primates, but the molecular structures of the two groups of NK cell receptors are very different. A hypothesis was presented to explain the origin of the differential use of Ly49 and KIR genes in rodents and primates. 相似文献
8.
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
9.
The 1q21 to 25 region of human chromosome 1 contains genes which encode proteins with immune- and inflammation-associated
functions. These include the pentraxin genes, for C-reactive protein (CRP), serum amyloid P (SAP) protein (APCS), and a CRP pseudogene (CRPP1). The region of chromosome 1 containing this cluster is syntenic with distal mouse chromosome 1. We constructed an approximately
1.4 megabase yeast artificial chromosome (YAC) contig with the pentraxin genes at its core. This four-YAC contig includes
other genes with immune functions including the FCER1A gene, which encodes the α-subunit of the IgE high-affinity Fc receptor and the IFI-16 gene, an interferon-γ-induced gene. In addition, it contains the histone H3F2 and H4F2 genes and the gene for erythroid α-spectrin (SPTA1). The gene order is cen.-SPTA1-H4F2-H3F2-IFI-16-CRP-CRPP1-APCS-FCER1A- tel. The contig thus consists of a cluster of genes whose products either have immunological importance, bind DNA, or both.
Received: 13 December 1995 / 6 February 1996 相似文献
10.
C. M. Ronning J. R. Stommel S. P. Kowalski L. L. Sanford R. S. Kobayashi O. Pineada 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1999,98(1):39-46
Solanum chacoense Bitter, a wild relative of the cultivated potato, produces several glycoalkaloids, including solanine, chaconine, and the
leptines. The foliar-specific leptine glycoalkaloids are believed to confer resistance to the Colorado Potato Beetle (CPB).
Using two bulked DNA samples composed of high- and low-percent leptine individuals from a segregating F1 population of S. chacoense, we have identified two molecular markers that are closely linked to high percent solanine+chaconine and, conversely, to
nil/low percent leptine. One of these, a 1,500-bp RAPD product (UBC370-1500), had a recombination value of 3% in the F1 progeny, indicating tight linkage. UBC370-1500 mapped to the end of the short arm of potato chromosome 1, in the region of
a previously mapped major QTL for solanidine, from a S. tuberosum (solanidine)×S. berthaultii (solasodine) cross. Taken together, these results suggest that either (1) a major locus determining solanidine accumulation
in Solanum spp. is on chromosome 1 in the region defined by the RFLP markers TG24, CT197, and CT233, or (2) this region of chromosome
1 may harbor two or more important genes which determine accumulation of steroidal aglycones. These findings are important
for the genetics of leptine (as well as other glycoalkaloid) accumulation and for the development of CPB-resistant potato
varieties.
Received: 5 March 1998 / Accepted: 28 July 1998 相似文献
11.
Ann Lövgren Cathrine R. Carlson Katarina Eskils Anne-Brit Kolstø 《Current microbiology》1998,37(4):245-250
The insect pathogen Bacillus thuringiensis (Bt) has earlier been shown to possess virulence factors in addition to the crystal toxins. Bt subsp. gelechiae strain Bt13 lacks crystals but is still virulent to lepidopteran insects. Among the virulence co-expressed genes are two
phospholipases; phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphatidylcholine-degrading phospholipase C (PC-PLC),
flagellin, and β-lactamase I. In addition to these putative virulence factors the toxic neutral metalloprotease immune inhibitor
A (InA) has been identified. In this paper we report a circular 5.9 Mb combined physical and genetic map of the of the Bt
subsp. gelechiae chromosome. The genes encoding PI-PLC, PC-PLC, InA, flagellin, and β-lactamase I are shown to be scattered over the chromosome.
The PLC-encoding genes have been cloned from Bt13, and DNA sequencing showed that the Bt subsp. gelechiae PLC genes are >90% identical to their previously cloned equivalents from Bt or B. cereus. An HD-1 crystal toxin (cryIA) gene probe was found to hybridize to the Bt13 chromosome, but not to extrachromosomal elements.
Received: 26 March 1998 / Accepted: 6 May 1998 相似文献
12.
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
13.
E. Huq S. Harrington M. A. Hossain F. Wen S. R. McCouch T. K. Hodges 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1999,98(5):815-824
The anaerobic fermentation pathway is thought to play an important role under flooding conditions. The pyruvate decarboxylase
2 (pdc2) gene that encodes the first enzyme of this pathway has been cloned and characterized from rice. This gene has an open reading
frame that putatively encodes a 603 amino-acid-residue protein with a molecular mass of 64 kDa. pdc2 has five introns dispersed throughout the coding region, which is also true for rice pdc1. Although the length of these introns in rice pdc2 are different from those in rice pdc1, they are located in exactly the same positions based on the deduced amino-acid sequences. The temporal and spatial expression
patterns of pdc1 and pdc2 show that pdc2 is induced to a higher level during the early period (1.5–12 h) of anoxia than pdc1, which is induced more after longer time periods (24–72 h) of anoxia in both shoots and roots. The map positions of the three
pdc genes have also been determined. Rice pdc1 is located on chromosome 5 between BCD454A and RZ67, pdc2 is located on chromosome 3 between RZ329 and RZ313, and pdc3 is mapped on chromosome 7 distal to RG351.
Received: 19 May 1998 / Accepted: 29 September 1998 相似文献
14.
We have isolated two yeast artificial chromosome (YAC) clones from Drosophila melanogaster that contain a small amount of dodeca satellite (a satellite DNA located in the centromeric region of chromosome 3) and sequences homologous to the telomeric retrotransposon HeT-A. Using these YACs as probes for fluorescence in situ hybridization
to mitotic chromosomes, we have localized these HeT-A elements to the centric heterochromatin of chromosome 3, at region h55. The possible origin of these telomeric elements in a centromeric position is discussed.
Received: 30 July 1999 / Accepted: 19 September 1999 相似文献
15.
“Candidatus Liberobacter,” the uncultured bacterium associated with citrus Huanglongbing (HLB) disease, is an α-Proteobacteria, and two species, “Candidatus L. africanum” and “Candidatus L. asiaticum,” have been characterized by sequence analysis of the 16S rDNA and β operon (rplKAJL-rpoBC) genes. These genes were isolated by PCR and random cloning of DNA from infected plants. However, this strategy is laborious
and allowed selection of only three Liberobacter DNA fragments. In this paper, we described isolation of additional genes
using Random Amplified Polymorphic DNA (RAPD). In total, 102 random 10-mer primers were used in PCR reactions on healthy and
Liberobacter-infected plant DNA. Eight DNA bands amplified from infected plant DNA were cloned and analyzed. Six of them were
found to be part of the Liberobacter genome by sequence and hybridization experiments. On these DNA fragments, four genes
were identified: nusG, pgm, omp, and a hypothetical protein gene. These results indicate that RAPD can be used to clone DNA of uncultured organisms.
Received: 14 September 1998 / Accepted: 6 October 1998 相似文献
16.
Nicole Rempel Sibilla Heyers Hartmut Engels E. Sleegers O. K. Steinlein 《Human genetics》1998,103(6):645-653
The α4-subunit gene (CHRNA4) of the neuronal nicotinic acetylcholine receptor (nAChR) subunit family has recently been identified in two families as
the gene responsible for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), a rare monogenic idiopathic epilepsy.
As a result of this finding, other subunits of the neuronal nAChR gene family are being considered as candidate genes for
ADNFLE in families not linked to CHRNA4 and for other idiopathic epilepsies. α4-subunitsoften assemble together with β2-subunits (gene symbol CHRNB2) to build heteromeric nAChRs. The gene encoding another abundant AChR subunit, the α3-subunit gene (CHRNA3), is present with those encoding two other subunits, CHRNB4 and CHRNA5, in a gene cluster whose functional role is still
unclear. Here we provide the information on the genomic structures of both the CHRNB2 and the CHRNA3 genes that is necessary for comprehensive mutational analyses, and we refine the genomic assignment of CHRNB2 on chromosome 1.
Received: 5 August 1998 / Accepted: 13 October 1998 相似文献
17.
Background
The centromeres in yeast (S. cerevisiae) are organized by short DNA sequences (125 bp) on each chromosome consisting of 2 conserved elements: CDEI and CDEIII spaced by a CDEII region. CDEI and CDEIII are critical sequence specific protein binding sites necessary for correct centromere formation and following assembly with proteins, are positioned near each other on a specialized nucleosome. Hegemann et al. BioEssays 1993, 15: 451–460 reported single base DNA mutants within the critical CDEI and CDEIII binding sites on the centromere of chromosome 6 and quantitated centromere loss of function, which they measured as loss rates for the different chromosome 6 mutants during cell division. Olson et al. Proc Natl Acad Sci USA 1998, 95: 11163–11168 reported the use of protein-DNA crystallography data to produce a DNA dinucleotide protein deformability energetic scale (PD-scale) that describes local DNA deformability by sequence specific binding proteins. We have used the PD-scale to investigate the DNA sequence dependence of the yeast chromosome 6 mutants' loss rate data. Each single base mutant changes 2 PD-scale values at that changed base position relative to the wild type. In this study, we have utilized these mutants to demonstrate a correlation between the change in DNA deformability of the CDEI and CDEIII core sites and the overall experimentally measured chromosome loss rates of the chromosome 6 mutants. 相似文献18.
19.
Construction of a bacterial artificial chromosome library of Medicago truncatula and identification of clones containing ethylene-response genes 总被引:6,自引:0,他引:6
Y.-W. Nam R. V. Penmetsa G. Endre P. Uribe D. Kim D. R. Cook 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1999,98(3-4):638-646
To facilitate genome analysis and map-based cloning of symbiotic genes in the model legume Medicago truncatula, a bacterial artificial chromosome (BAC) library was constructed. The library consists of 30 720 clones with an average insert
size of approximately 100 kb, representing approximately five haploid-genome equivalents. The frequency of BAC clones carrying
inserts of chloroplast DNA was estimated to be 1.4%. Screening of the library with single- or low-copy genes as hybridization
probes resulted in the detection of 1–12 clones per gene. Hybridization of the library with repeated sequences such as rDNA
genes and transposon-like elements of M. truncatula revealed the presence of 60 and 374 BAC clones containing the two sequences, respectively. The BAC library was pooled for
screening by polymerase chain reaction (PCR)-amplification. To demonstrate the utility of this system, we used primers designed
from a conserved region of the ein3-like loci of Arabidopsis thaliana and isolated six unique BAC clones from the library. DNA gel-blot and sequence analyses showed that these ein3-like clones could be grouped into three classes, an observation consistent with the presence of multiple ein3-like loci in M. truncatula. These results indicate that the BAC library represents a central resource for the map-based cloning and physical mapping
in M. truncatula and other legumes.
Received: 27 July 1998 / Accepted: 5 August 1998 相似文献
20.
J. Casqueiro S. Gutiérrez O. Ba?uelos F. Fierro J. Velasco J. F. Martín 《Molecular & general genetics : MGG》1998,259(5):549-556
A DNA fragment containing a gene homologous to LYS2 gene of Saccharomyces cerevisiae was cloned from a genomic DNA library of Penicillium chrysogenum AS-P-78. It encodes a protein of 1409 amino acids (Mr^ 154 859) with strong similarity to the S. cerevisiae (49.9% identity) Schizosaccharomycespombe (51.3% identity) and Candida albicans (48.12% identity) α-aminoadipate reductases and a lesser degree of identity to the amino acid-activating domains of the non-ribosomal
peptide synthetases, including the α-aminoadipate-activating domain of the α-aminoadipyl-cysteinyl-valine synthetase of P. chrysogenum (12.4% identical amino acids). The lys2 gene contained one intron in the 5′-region and other in the 3′-region, as shown by comparing the nucleotide sequences of
the cDNA and genomic DNA, and was transcribed as a 4.7-kb monocistronic mRNA. The lys2 gene was localized on chromosome III (7.5 Mb) in P. chrysogenum AS-P-78 and on chromosome IV (5.6 Mb) in strain P2, whereas the penicillin gene cluster is known to be located in chromosome
I in both strains. The lys2-encoded protein is a member of the aminoacyladenylate-forming enzyme family with a reductase domain in its C-terminal region.
Received: 26 January 1998 / Accepted: 4 May 1998 相似文献