Abstract:
:Beta-2 microglobulin (B2M) is a component of the major histocompatibility complex (MHC) class I molecule and has been studied as a biomarker of kidney function, cardiovascular diseases and mortality. Little is known about the genes influencing its levels directly or through glomerular filtration rate (GFR). We conducted a genome-wide association study of plasma B2M levels in 6738 European Americans from the Atherosclerosis Risk in Communities study to identify novel loci for B2M and assessed its association with known estimated GFR (eGFR) loci. We identified 2 genome-wide significant loci. One was in the human leukocyte antigen (HLA) region on chromosome 6 (lowest p value = 1.8 × 10(-23) for rs9264638). At this locus, 6 index SNPs accounted for 3.2 % of log(B2M) variance, and their association with B2M could largely be explained by imputed classical alleles of the MHC class I genes: HLA-A, HLA-B, or HLA-C. The index SNPs at this locus were not associated with eGFR based on serum creatinine (eGFRcr). The other locus of B2M was on chromosome 12 (rs3184504 at SH2B3, beta = 0.02, p value = 3.1 × 10(-8)), which was previously implicated as an eGFR locus. In conclusion, although B2M is known to be a component of MHC class I molecule, the association between HLA class I alleles and plasma B2M levels in a community-based population is novel. The identification of the two novel loci for B2M extends our understanding of its metabolism and informs its use as a kidney filtration biomarker.
journal_name
Hum Genetjournal_title
Human geneticsauthors
Tin A,Astor BC,Boerwinkle E,Hoogeveen RC,Coresh J,Kao WHdoi
10.1007/s00439-013-1274-7subject
Has Abstractpub_date
2013-06-01 00:00:00pages
619-27issue
6eissn
0340-6717issn
1432-1203journal_volume
132pub_type
杂志文章相关文献
HUMAN GENETICS文献大全abstract::A simple routine method for detecting individuals who are heterozygous for the silent gene Gt 0 is presented. This method consists of a combination of electrophoresis and densitometry. The results confirm the theoretical expectation that these individuals would exhibit about 50% of the enzyme activity found in the cor...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00278984
更新日期:1980-01-01 00:00:00
abstract::Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disease characterized by enlarged kidneys and congenital hepatic fibrosis. Given the poor prognosis for the majority of children with the severe perinatal ARPKD phenotype, there is a regular request for prenatal testing. ARPKD ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-005-0027-7
更新日期:2005-11-01 00:00:00
abstract::By screening patients with autosomal dominant retinitis pigmentosa for mutations in the rhodopsin gene, two deletions (8 bp and 1 bp) have been identified in exon 5; these deletions cause a shift in the reading frame. The predicted proteins should be radically altered with translation continuing past the normal stop s...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00220073
更新日期:1992-11-01 00:00:00
abstract::The predisposing genetic defect in multiple endocrine neoplasia type 1 has been assigned to chromosomal region 11q13. Our previous attempts to identify the MEN1 gene have resulted in the isolation of the phospholipase C beta 3 gene from the actual region. PLCB3 plays an important role in signal transduction and, moreo...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050326
更新日期:1997-01-01 00:00:00
abstract::Mutations in the GJB2 gene have been identified in many patients with childhood deafness, 35delG being the most common mutation in Caucasoid populations. We have analyzed a total of 576 families/unrelated patients with recessive or sporadic deafness from Italy and Spain, 193 of them being referred as autosomal recessi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390051007
更新日期:2000-01-01 00:00:00
abstract::A pachytene chromomere map of bivalent 10 is presented. Recent results from high-resolution metaphase banding document a similar pattern of intrachromosomal differentiation. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00271567
更新日期:1979-11-01 00:00:00
abstract::Cytogenetic analysis of 26 non-Burkitt lymphomas having abnormal clones, revealed non-random involvement of certain chromosomes in numerical and structural changes. In some cases, chromosome structural abnormalities could be correlated with histopathology of the tumours. A combined analysis of cases in the present ser...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00287055
更新日期:1980-01-01 00:00:00
abstract::Thirty-nine recombinants isolated from a Y chromosome-specific library were deletion mapped. Seven deletion intervals were defined by hybridization of probes to DNA of eight individuals with aberrant Y chromosomes. Extreme cytogenetic limits of the deletion intervals were determined by in situ hybridization of one pro...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00193197
更新日期:1990-07-01 00:00:00
abstract::Therapeutic interventions that lower LDL-cholesterol effectively reduce the risk of coronary artery disease (CAD). However, statins, the most widely prescribed LDL-cholesterol lowering drugs, increase diabetes risk. We used genome-wide association study (GWAS) data in the public domain to investigate the relationship ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-016-1647-9
更新日期:2016-05-01 00:00:00
abstract::As evidenced by a large pedigree with 21 affected members, acrokeratoelastoidosis (AKE) is an autosomal dominant skin disease (10185; McKusick 1978). Linkage with genetic markers already assigned to human chromosomes could help to map the gene for this disease. Therefore 22 markers were investigated in 61 members of t...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00284653
更新日期:1983-01-01 00:00:00
abstract::Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here a systematic mutational screening of the mitochondrial 12S rRNA gene in 128 Chinese pediatric subjects with sporadic aminoglycoside-induced and non-syndromic hearing loss. We show that aminoglycoside...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-005-1276-1
更新日期:2005-06-01 00:00:00
abstract::The homeodomain transcription factors (TFs) Pax6 (OMIM: 607108) and Prox1 (OMIM: 601546) critically regulate gene expression in lens development. While PAX6 mutations in humans can cause cataract, aniridia, microphthalmia, and anophthalmia, among other defects, Prox1 deletion in mice causes severe lens abnormalities, ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-020-02195-7
更新日期:2020-12-01 00:00:00
abstract::The aim of this study was to estimate the risk of viable unbalanced offspring for a parental carrier of reciprocal translocation. On a large computerized database of reciprocal translocations we used logistic regression to model this risk. The status of the progeny is the outcome variable. Explanatory covariates are c...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00420946
更新日期:1993-12-01 00:00:00
abstract::Congenital heart disease (CHD) affects over 40% of Down syndrome (DS) patients. The region proposed to contain the gene(s) for DS CHD has been restricted to 21q22.2-22.3, from D21S55 to MX1. The identification and functional characterization of the genes mapping to this region is a necessary step to understand the pat...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050693
更新日期:1998-03-01 00:00:00
abstract::Whole genome sequencing (WGS) was performed to identify the variants responsible for inherited retinal degeneration (IRD) in a Caucasian family. Segregation analysis of selected rare variants with pathogenic potential identified a set of compound heterozygous changes p.Arg266*:c.796C>T and p.Ala568Thr:c.1702G>A in the...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-018-1897-9
更新日期:2018-07-01 00:00:00
abstract::Hybrids were performed between cell lines derived from four patients with Fanconi's anemia in which different biochemical lesions have been postulated. Complementation studies in these hybrids based on the rate of mitomycin C-induced chromosomal damage supported the concept of allelic mutations. It was therefore concl...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00289479
更新日期:1983-01-01 00:00:00
abstract::Trichorhinophalangeal syndrome type I (TRPS I) is a rare autosomal dominant syndrome caused by haploinsufficiency of TRPS1 due to point mutations or deletions. Here, we report the first familial TRPS I due to a t(8;13)(q23.3;q21.31) translocation breakpoint <100 kb from the 5' end of TRPS1. Based on the additional abn...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-013-1333-0
更新日期:2013-11-01 00:00:00
abstract::We have identified a rare polymorphism (G to C at nucleotide 1102) in CYBB, which codes for gp91-phox, a component of NADPH oxidase. Polymorphonuclear leukocytes with this enzyme produced normal amounts of superoxide anion. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF02281870
更新日期:1996-05-01 00:00:00
abstract::A method is introduced for simultaneously using multiple loci to estimate admixture and test goodness of fit of the model of admixture. Deviation of observed frequencies from expectation caused by sources of error such as sampling and/or drift is allowed for all loci in all populations. This allows investigation of th...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291407
更新日期:1984-01-01 00:00:00
abstract::Esterase D levels from 200 retinoblastoma patients have been measured in an attempt to identify individuals carrying deletions of chromosome region 13q14. In this series 75% had bilateral tumours and 23% were familial. Of nine patients identified as having low esterase D levels, five had not previously been diagnosed ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00283938
更新日期:1986-02-01 00:00:00
abstract::Using a heteroduplex approach and direct sequencing, we have completed the screening of approximately 88% of the neurofibromatosis type 2 (NF2)-coding sequence of DNA extracted from 33 schwannomas from NF2 patients and from 29 patients with sporadic schwannomas. The extensive screening has resulted in the identificati...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050188
更新日期:1996-08-01 00:00:00
abstract::Heteromorphisms of chromosomes 1, 9, and 16 were studied by C-banding in a population of 403 mentally retarded individuals from diverse ethnic groups. A significant difference in the distribution of heteromorphisms was found among the different racial groups. The Orientals had a larger C-band on chromosome 1 and a sma...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00277571
更新日期:1978-11-24 00:00:00
abstract::Genome-wide association studies (GWAS) have identified a large number of disease-associated SNPs, but in few cases the functional variant and the gene it controls have been identified. To systematically identify candidate regulatory variants, we sequenced ENCODE cell lines and used public ChIP-seq data to look for tra...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-016-1654-x
更新日期:2016-05-01 00:00:00
abstract::A total of 362 males from various regions of Papua New Guinea were screened for red cell glucose-6-phosphate dehydrogenase (G6PD) activity. Twenty-six G6PD deficient individuals were identified. Biochemical characterization of G6PD purified from these subjects has revealed 13 new variants and several copies of previou...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00569710
更新日期:1982-01-01 00:00:00
abstract::A cytogenetic follow-up has been made of nine mixoploid children found among 11 148 consecutive newborn children. The frequency of the cell line with normal chromosomes increased in all but two, and the increase was statistically significant, being from 20% to 39% in four cases, and from 1% to 17% in three, while in o...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00290218
更新日期:1980-01-01 00:00:00
abstract::Cytogenetic preparations from oocytes remaining unfertilised after in vitro fertilisation revealed single chromatids (as opposed to whole chromosomes) in 4 out of 38 meiosis II metaphases. In one oocyte, a single chromatid was present in addition to the normal 23,X complement, and in three oocytes, two identical but s...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00201839
更新日期:1991-02-01 00:00:00
abstract::African Americans have increased susceptibility to non-diabetic (non-DM) forms of end-stage renal disease (ESRD) and extensive evidence supports a genetic contribution. A genome-wide association study (GWAS) using pooled DNA was performed in 1,000 African Americans to detect associated genes. DNA from 500 non-DM ESRD ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-010-0842-3
更新日期:2010-08-01 00:00:00
abstract::Mouse mutants are a long-lasting, valuable tool to identify genes underlying eye diseases, because the absence of eyes, very small eyes and severely affected, cataractous eyes are easily to detect without major technical equipment. In mice, actually 145 genes or loci are known for anophthalmia, 269 for microphthalmia,...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/s00439-019-01995-w
更新日期:2019-09-01 00:00:00
abstract::A locus (CPX) responsible for X-linked cleft palate and ankyloglossia was previously mapped to the proximal long arm of the X chromosome through DNA marker linkage studies in two large kindred: an Icelandic family and a British Columbia (B.C.) Native family. In this study, additional linkage analyses have been perform...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00202859
更新日期:1994-08-01 00:00:00
abstract::Disease-causing mutations have been identified in various entities of autosomal dominant ataxia and in Friedreich's ataxia. However, no molecular pathogenic factor is known to cause idiopathic cerebellar ataxias. We investigated the CAG/CTG trinucleotide repeats causing spinocerebellar ataxia types 1, 2, 3, 6, 7, 8 an...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390000346
更新日期:2000-08-01 00:00:00