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241.
PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans
Grall A Guaguère E Planchais S Grond S Bourrat E Hausser I Hitte C Le Gallo M Derbois C Kim GJ Lagoutte L Degorce-Rubiales F Radner FP Thomas A Küry S Bensignor E Fontaine J Pin D Zimmermann R Zechner R Lathrop M Galibert F André C Fischer J 《Nature genetics》2012,44(2):140-147
Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family. 相似文献
242.
Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas 总被引:1,自引:0,他引:1
Wu G Broniscer A McEachron TA Lu C Paugh BS Becksfort J Qu C Ding L Huether R Parker M Zhang J Gajjar A Dyer MA Mullighan CG Gilbertson RJ Mardis ER Wilson RK Downing JR Ellison DW Zhang J Baker SJ;St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project 《Nature genetics》2012,44(3):251-253
To identify somatic mutations in pediatric diffuse intrinsic pontine glioma (DIPG), we performed whole-genome sequencing of DNA from seven DIPGs and matched germline tissue and targeted sequencing of an additional 43 DIPGs and 36 non-brainstem pediatric glioblastomas (non-BS-PGs). We found that 78% of DIPGs and 22% of non-BS-PGs contained a mutation in H3F3A, encoding histone H3.3, or in the related HIST1H3B, encoding histone H3.1, that caused a p.Lys27Met amino acid substitution in each protein. An additional 14% of non-BS-PGs had somatic mutations in H3F3A causing a p.Gly34Arg alteration. 相似文献
243.
244.
A population of the dwarf bear-poppy ( Arctomecon humilis Coville, Papaveraceae) at Red Bluff, Washington County, Utah, was monitored twice annually between 1987 and 2002. This is a narrowly endemic, gypsophilous species that has been formally listed as endangered since 1979. During the 16 years of observation, density of this species has fluctuated between 3 and 1336 individuals on the 0.07-ha monitoring plot. Moderate to large recruitments of seedlings occurred in 1992, 1995, and 2001. Seedling recruitments from a large, long-lived seed bank are triggered by abundant precipitation during the February-April period. At least 5.0 cm of rainfall is required during that interval to produce any seedlings. Seedlings experienced considerable mortality in the 1st few months of life in all observed cases. The average seedling initiated in the very large recruitment event of 1992 survived for only 2.6 years. Seedlings in that cohort that were alive 1 year after germination had an average longevity of 4.6 years. None of the seedlings that emerged in 1992 were still alive in October 2002. Mortality in this species was poorly correlated with fluctuations in precipitation or temperature. No epidemics of parasites or herbivores were observed. Mortality in the species appears to be caused by a variety of factors acting over a cohort's lifetime. 相似文献
245.
Becker-Heck A Zohn IE Okabe N Pollock A Lenhart KB Sullivan-Brown J McSheene J Loges NT Olbrich H Haeffner K Fliegauf M Horvath J Reinhardt R Nielsen KG Marthin JK Baktai G Anderson KV Geisler R Niswander L Omran H Burdine RD 《Nature genetics》2011,43(1):79-84
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with the abnormal function of motile cilia. Approximately half of individuals with PCD also have alterations in the left-right organization of their internal organ positioning, including situs inversus and situs ambiguous (Kartagener's syndrome). Here, we identify an uncharacterized coiled-coil domain containing a protein, CCDC40, essential for correct left-right patterning in mouse, zebrafish and human. In mouse and zebrafish, Ccdc40 is expressed in tissues that contain motile cilia, and mutations in Ccdc40 result in cilia with reduced ranges of motility. We further show that CCDC40 mutations in humans result in a variant of PCD characterized by misplacement of the central pair of microtubules and defective assembly of inner dynein arms and dynein regulatory complexes. CCDC40 localizes to motile cilia and the apical cytoplasm and is required for axonemal recruitment of CCDC39, disruption of which underlies a similar variant of PCD. 相似文献
246.
Wright FA Strug LJ Doshi VK Commander CW Blackman SM Sun L Berthiaume Y Cutler D Cojocaru A Collaco JM Corey M Dorfman R Goddard K Green D Kent JW Lange EM Lee S Li W Luo J Mayhew GM Naughton KM Pace RG Paré P Rommens JM Sandford A Stonebraker JR Sun W Taylor C Vanscoy LL Zou F Blangero J Zielenski J O'Neal WK Drumm ML Durie PR Knowles MR Cutting GR 《Nature genetics》2011,43(6):539-546
A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10(-8)) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del homozygotes (P = 0.006) from a separate family based study (n = 557), with P = 1.49 × 10(-9) for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family based study identified a significant quantitative trait locus on chromosome 20q13.2 (log(10) odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder. 相似文献
247.
Macgregor S Montgomery GW Liu JZ Zhao ZZ Henders AK Stark M Schmid H Holland EA Duffy DL Zhang M Painter JN Nyholt DR Maskiell JA Jetann J Ferguson M Cust AE Jenkins MA Whiteman DC Olsson H Puig S Bianchi-Scarrà G Hansson J Demenais F Landi MT Dębniak T Mackie R Azizi E Bressac-de Paillerets B Goldstein AM Kanetsky PA Gruis NA Elder DE Newton-Bishop JA Bishop DT Iles MM Helsing P Amos CI Wei Q Wang LE Lee JE Qureshi AA Kefford RF Giles GG Armstrong BK Aitken JF Han J Hopper JL Trent JM Brown KM 《Nature genetics》2011,43(11):1114-1118
We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density. 相似文献
248.
Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters 总被引:5,自引:0,他引:5
249.
A rare penetrant mutation in CFH confers high risk of age-related macular degeneration 总被引:1,自引:0,他引:1
250.
Hahn CN Chong CE Carmichael CL Wilkins EJ Brautigan PJ Li XC Babic M Lin M Carmagnac A Lee YK Kok CH Gagliardi L Friend KL Ekert PG Butcher CM Brown AL Lewis ID To LB Timms AE Storek J Moore S Altree M Escher R Bardy PG Suthers GK D'Andrea RJ Horwitz MS Scott HS 《Nature genetics》2011,43(10):1012-1017