Abstract:
:B-cell receptors (BCRs) play a critical role in adaptive immunity as they generate highly diverse immunoglobulin repertoires to recognize a wide variety of antigens. To better understand immune responses, it is critically important to establish a quantitative and rapid method to analyze BCR repertoire comprehensively. Here, we developed "Bcrip", a novel approach to characterize BCR repertoire by sequencing millions of BCR cDNA using next-generation sequencer. Using this method and quantitative real-time PCR, we analyzed expression levels and repertoires of BCRs in a total of 17 peanut allergic subjects' peripheral blood samples before and after receiving oral immunotherapy (OIT) or placebo. By our methods, we successfully identified all of variable (V), joining (J), and constant (C) regions, in an average of 79.1% of total reads and 99.6% of these VJC-mapped reads contained the C region corresponding to the isotypes that we aimed to analyze. In the 17 peanut allergic subjects' peripheral blood samples, we observed an oligoclonal enrichment of certain immunoglobulin heavy chain alpha (IGHA) and IGH gamma (IGHG) clones (P = 0.034 and P = 0.027, respectively) in peanut allergic subjects after OIT. This newly developed BCR sequencing and analysis method can be applied to investigate B-cell repertoires in various research areas, including food allergies as well as autoimmune and infectious diseases.
journal_name
J Hum Genetjournal_title
Journal of human geneticsauthors
Kiyotani K,Mai TH,Yamaguchi R,Yew PY,Kulis M,Orgel K,Imoto S,Miyano S,Burks AW,Nakamura Ydoi
10.1038/s10038-017-0364-0subject
Has Abstractpub_date
2018-02-01 00:00:00pages
239-248issue
2eissn
1434-5161issn
1435-232Xpii
10.1038/s10038-017-0364-0journal_volume
63pub_type
杂志文章,多中心研究,随机对照试验abstract::Multiple genomic disorders result from recurrent deletions or duplications between low copy repeat (LCR) clusters, mediated by nonallelic homologous recombination. These copy number variants (CNVs) often exhibit variable expressivity and/or incomplete penetrance. However, the population prevalence of many genomic diso...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-018-0451-x
更新日期:2018-07-01 00:00:00
abstract::Mutations in BRCA genes elevate risk for breast and ovarian cancer. These mutations are population specific. As there are no data on BRCA mutation screening on larger number of probands in Serbia to date, aim of this study was to determine types and frequencies of BRCA mutations in individuals from high-risk families ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2013.30
更新日期:2013-08-01 00:00:00
abstract::We report the case of a 12 year-old boy with oto-palato-digital syndrome type II (OPD II). He had various anomalies at birth, including bilateral cataracts, bilateral glaucoma, bilateral severe hearing impairment, congenital heart defect, umbilical herniation, bowed extremities and constrictions of various joints. The...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0108-7
更新日期:2007-01-01 00:00:00
abstract::We used magnetic resonance imaging (MRI) to examine the brain of a typical Coffin-Lowry syndrome (CLS) patient. There were many small perivascular focal areas of hypointensity in the white matter on T1-weighted images, similar to those found in mucopolysaccharidosis or perivascular leukomalacia. However, these changes...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050038
更新日期:1998-01-01 00:00:00
abstract::As a result of the combination of great linguistic and cultural diversity, the highland populations of Daghestan present an excellent opportunity to test the hypothesis of language-gene coevolution at a fine geographic scale. However, previous genetic studies generally have been restricted to uniparental markers and h...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2015.132
更新日期:2016-03-01 00:00:00
abstract::Pseudoautosomal region 1 (PAR1) contains SHOX, in addition to seven highly conserved non-coding DNA elements (CNEs) with cis-regulatory activity. Microdeletions involving SHOX exons 1-6a and/or the CNEs result in idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD). Here, we report six rare copy-numbe...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2015.53
更新日期:2015-09-01 00:00:00
abstract::Although the Japanese population has a rather low genetic diversity, we recently confirmed the presence of two main clusters (the Hondo and Ryukyu clusters) through principal component analysis of genome-wide single-nucleotide polymorphism (SNP) genotypes. Understanding the genetic differences between the two main clu...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2012.26
更新日期:2012-05-01 00:00:00
abstract::Intracranial aneurysm (IA) is characterized by an abnormal bulging of one of the arteries in the brain and is heavily affected by genetic factors. Although IA is a very serious disease because of its severity and prevalence in the general public, the gene causing IA has not yet been identified due mainly to the lack o...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2011.27
更新日期:2011-06-01 00:00:00
abstract::The genomes of outbred populations were first shown in 2006 to contain regions of homozygosity (ROHs) of several megabases. Further studies have also investigated the characteristics of ROHs in healthy individuals in various populations but there are no studies on Singapore populations to date. This study aims to iden...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2011.132
更新日期:2012-02-01 00:00:00
abstract::Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disease with autosomal dominant transmission characterized by the presence of malformations of the big toes and of postnatal progressive heterotopic endochondral osteogenesis. We report the case of 3-year-old girl with dysplasia of the first metatarsal b...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-006-0069-2
更新日期:2006-01-01 00:00:00
abstract::GNE myopathy is a rare autosomal recessive distal myopathy caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), the bi-functional enzyme critical for sialic acid biosynthesis. In this study, we summarized the clinical features, pathological characteristics, and genetic profiles ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-018-0525-9
更新日期:2019-01-01 00:00:00
abstract::Variation in the human monoamine oxidase A (MAO-A) gene can influence neurotransmittor levels and is thought to have a role in many behavioral traits. The genetic architecture of MAO-A is known to vary across different geographic subgroups. Previous studies have reported evidence for positive selection within the MAO-...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2012.19
更新日期:2012-05-01 00:00:00
abstract::Recently, pharmacological chaperone therapy for Pompe disease with small molecules such as imino sugars has attracted interest. But mutant acid α-glucosidase (GAA) species responsive to imino sugars are limited. To elucidate the characteristics of a mutant GAA responsive to imino sugars, we performed biochemical and s...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2011.36
更新日期:2011-06-01 00:00:00
abstract::Androgen insensitivy syndrome (AIS) is the most frequent cause of male pseudohermaphroditism resulting from target-organ resistance to androgen action. Individuals bearing the complete form of the disease (CAIS) present a female phenotype and a lack of pubic and axillary hair. In the present study, four 46,XY patients...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-003-0036-0
更新日期:2003-01-01 00:00:00
abstract::Disrupted-in-schizophrenia 1 (DISC1) was reported to be associated with schizophrenia. In a previous study, we found significant association with schizophrenia patients with deficient sustained attention assessed by continuous performance test (CPT). This study aimed to identify risk polymorphisms in this specific neu...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-019-0597-1
更新日期:2019-07-01 00:00:00
abstract::Most studies on the genetic basis of human skin pigmentation have focused on people of European ancestry and only a few studies have focused on Asian populations. We investigated the association of skin reflectance and freckling with genetic variants of melanocortin 1 receptor (MC1R) gene in Japanese. DNA samples were...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2012.96
更新日期:2012-11-26 00:00:00
abstract::Chromosome 5, especially the 5q31-33 region, may contain one or more loci to control total serum IgE as well as asthma and bronchial hyperresponsiveness. To investigate the regions related with IgE level in chromosome 5, we performed a case-control association study on 105 high-IgE-level and 85 normal-IgE-level asthma...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-004-0215-7
更新日期:2005-01-01 00:00:00
abstract::Hereditary motor and sensory neuropathy with proximal dominancy (HMSN-P) is an adult-onset peripheral neurodegenerative disorder which has been reported only in the Okinawa Islands, Japan. The disease locus of "Okinawa-type" HMSN-P has been previously mapped to 3q13.1, with all affected individuals sharing an identica...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0193-7
更新日期:2007-01-01 00:00:00
abstract::Results of twin studies have shown that autism spectrum disorders (ASDs) are attributable to complex multigenic interactions rather than to a single susceptibility gene. However, the growing number of distinct, individually rare genetic causes of ASDs, mostly copy number variations (CNVs), favors an alternative to the...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2009.105
更新日期:2009-12-01 00:00:00
abstract::The KCNQ2 gene codifies a subunit of the voltage-gated potassium M channel underlying the neuronal M-current. Classically, mutations in this gene have been associated with benign familial neonatal seizures, however, in recent years KCNQ2 mutations have been reported associated to early-onset epileptic encephalopathy. ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2016.104
更新日期:2017-02-01 00:00:00
abstract::Mutations in the voltage-gated chloride/proton antiporter ClC-5 gene, CLCN5, are associated with Dent's disease, an X-linked renal tubulopathy. Our interest is to identify and characterize disease-causing CLCN5 mutations, especially those that alter the splicing of the pre-mRNA. We analyzed the CLCN5 gene from nine un...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0112-y
更新日期:2007-01-01 00:00:00
abstract::Following the recent completion of the human genome sequence, genomics research has shifted its focus to understanding gene complexity, expression, and regulation. However, in order to investigate such issues, there is a need to develop a practical system for genomic DNA expression. Transformation-associated recombina...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-005-0300-6
更新日期:2005-01-01 00:00:00
abstract::Fragile X syndrome (FXS) is a neurodevelopmental disorder and a leading monogenic form of cognitive impairment and autism. It is the most common form of inherited mental retardation in males and a significant cause of mental retardation in females. It is caused by the instability and subsequent expansion of the CGG re...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2010.140
更新日期:2011-01-01 00:00:00
abstract::X-linked inheritance is very rare and is estimated to account for only 1-5% of all nonsyndromic hearing loss cases. We found a multiplex family from China segregating with X-linked nonsyndromic hearing loss. After exclusive analysis of 10 common variations of three hearing loss-related genes, GJB2, mtDNA12srRNA and SL...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-018-0443-x
更新日期:2018-06-01 00:00:00
abstract::The pattern of X-chromosome inactivation (XCI) can affect the clinical severity of X-linked disorders in females. XCI pattern analysis has been conducted mainly by HUMARA assay, a polymerase chain reaction-based assay using a methylation-sensitive restriction enzyme. However, this assay examines the XCI ratio of the a...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-018-0415-1
更新日期:2018-05-01 00:00:00
abstract::CRISPR/Cas9-based tools have rapidly developed in recent years. These include CRISPR-based gene activation (CRISPRa) or inhibition (CRISPRi), for which there are libraries. CRISPR libraries for loss of function have been widely used to identify new biological mechanisms, such as drug resistance and cell survival signa...
journal_title:Journal of human genetics
pub_type: 杂志文章,评审
doi:10.1038/s10038-017-0376-9
更新日期:2018-02-01 00:00:00
abstract::Genetic factors, alone or in interaction with components of the diet, are thought to be involved in the development of the metabolic syndrome. The objective of our study was first to compare the frequency of the peroxisome proliferator-activated receptor (PPAR)alpha-L162V polymorphism in a sample of men with and witho...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-004-0177-9
更新日期:2004-01-01 00:00:00
abstract::Bradycardia is a trigger of ventricular arrhythmias in patients with arrhythmia including Brugada syndrome and long QT syndrome. The HCN4 channel controls the heart rate, and its mutations predispose to inherited sick sinus syndrome and long QT syndrome associated with bradycardia. We found a 4 base-insertion at the s...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2008.16
更新日期:2009-02-01 00:00:00
abstract::Biallelic polymorphisms on the Y chromosome have been extensively used to study the history, evolution, and migration patterns of world populations. In this study we screened 8.5 kb of Y chromosomal DNA for single nucleotide polymorphisms (SNPs) in a panel of 95 male individuals belonging to different haplogroups. Fiv...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-005-0357-2
更新日期:2006-01-01 00:00:00
abstract::Methylation-specific (MS) multiplex ligation-dependent probe amplification (MLPA) at two differentially methylated regions (DMRs) at chromosome 11p15, H19-DMR and LIT1-DMR, and microsatellite analysis for uniparental disomy (UPD) at chromosome 7 or 11, have been recommended for the genetic diagnosis of the Beckwith-Wi...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2013.67
更新日期:2013-09-01 00:00:00