Comprehensive evaluation of allele frequency differences of MC1R variants across populations.


:The melanocortin 1 receptor (MC1R), a member of the G protein-coupled receptors superfamily, mediates the response to melanocortins and is currently the best-described contributor to normal pigment variation in humans. A remarkably large number of natural polymorphisms, or variants, of the MC1R gene have been identified in different populations. Some of these variants have been associated with specific hair and skin color phenotypes, the presence of freckling, and melanoma and nonmelanoma skin cancer risk. Interestingly, some MC1R variants have been associated with skin cancer beyond their effects on pigmentation. Although the red hair color variants (RHC variants) have been associated with skin cancer risk in the Celtic population, studies in darkly-pigmented Caucasian populations have demonstrated the importance of non-RHC MC1R variants on skin cancer risk as well. We have reviewed and compared allele frequency differences of MC1R variants across geographic regions. We observed large differences in the distribution of variants across populations, with a prominent difference between lightly and darkly-pigmented individuals. Moreover, among Caucasian groups, there were seven variants (p.V60L, p.V92M, p.D84E, p.R151C, p.R160W, p.R163Q, and p.D294H) with significantly different allele frequencies. Exploring differences in allele frequencies of MC1R variants across populations with varying pigmentation and differing skin cancer risk may improve our understanding of the complex relationship between MC1R, pigmentation, and carcinogenesis.


Hum Mutat


Human mutation


Gerstenblith MR,Goldstein AM,Fargnoli MC,Peris K,Landi MT




Has Abstract


2007-05-01 00:00:00












  • Palindrome-mediated and replication-dependent pathogenic structural rearrangements within the NF1 gene.

    abstract::Palindromic sequences can form hairpin structures or cruciform extrusions, which render them susceptible to genomic rearrangements. A 197-bp long palindromic AT-rich repeat (PATRR17) is located within intron 40 of the neurofibromatosis type 1 (NF1) gene (17q11.2). Through comprehensive NF1 analysis, we identified six ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hsiao MC,Piotrowski A,Alexander J,Callens T,Fu C,Mikhail FM,Claes KB,Messiaen L

    更新日期:2014-07-01 00:00:00

  • The human SHOX mutation database.

    abstract::The human SHOX database has recently been established to provide clinicians and scientists access to a central source of information about all known SHOX mutations associated with short stature phenotypes such as idiopathic short stature, Lèri-Weill dyschondrosteosis, Langer syndrome, and Turner syndrome. So far, the ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Niesler B,Fischer C,Rappold GA

    更新日期:2002-11-01 00:00:00

  • Enzymatic mutation detection (EMD) of novel mutations (R565X and R1523X) in the FBN1 gene of patients with Marfan syndrome using T4 endonuclease VII.

    abstract::The Enzymatic Mutation Detection (EMDtrade mark) method is a streamlined and improved version of the original Enzymatic Cleavage of Mismatch (EMC) method. EMD is a fully homogeneous, rapid four step procedure that allows for detection and localization of mismatched or unmatched nucleotides within heteroduplex DNA. To ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Youil R,Toner TJ,Bull E,Bailey AL,Earl CD,Dietz HC,Montgomery RA

    更新日期:2000-07-01 00:00:00

  • Pathogenic mitochondrial tRNA mutations--which mutations are inherited and why?

    abstract::Mitochondrial transfer RNA (mt-tRNA) mutations are the commonest mitochondrial (mtDNA) mutations to cause human disease. The majority of mt-tRNA mutations are heteroplasmic and while some exhibit maternal transmission within families, many others are only seen as sporadic mutations. Using the available clinical, bioch...

    journal_title:Human mutation

    pub_type: 杂志文章,meta分析


    authors: Elson JL,Swalwell H,Blakely EL,McFarland R,Taylor RW,Turnbull DM

    更新日期:2009-11-01 00:00:00

  • Structural assessment of single amino acid mutations: application to TP53 function.

    abstract::Single amino acid substitution is the type of protein alteration most related to human diseases. Current studies seek primarily to distinguish neutral mutations from harmful ones. Very few methods offer an explanation of the final prediction result in terms of the probable structural or functional effect on the protei...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Yip YL,Zoete V,Scheib H,Michielin O

    更新日期:2006-09-01 00:00:00

  • Detection of sequence variants in the gene for human type II procollagen (COL2A1) by direct sequencing of polymerase chain reaction-amplified genomic DNA.

    abstract::The direct sequencing of the human type II procollagen (COL2A1) gene from polymerase chain reaction (PCR)-amplified genomic DNA is described. Thirty-two regions of the COL2A1 gene were asymmetrically amplified with intron primers which were specifically chosen to amplify a region spanning 500 to 800 bp of sequence enc...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Williams CJ,Harrison DA,Hopkinson I,Baldwin CT,Ahmad NN,Ala-Kokko L,Korn RM,Buxton PG,Dimascio J,Considine EL

    更新日期:1992-01-01 00:00:00

  • Fanconi anemia A due to a novel frameshift mutation in hotspot motifs: lack of FANCA protein.

    abstract::Homozygosity for a frameshift mutation at codon 1213 of FANCA gene was identified in a Turkish patient. Immunoprecipitation-western blot analysis showed the complete absence of the FANCA protein band. This novel mutation, a deletion of T at position 3639 in exon 37 (3639delT), is responsible for the disease and causes...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Balta G,de Winter JP,Kayserili H,Pronk JC,Joenje H

    更新日期:2000-06-01 00:00:00

  • Mutation spectrum in patients with Rett syndrome in the German population: Evidence of hot spot regions.

    abstract::Mutations in the MECP2 (Methyl-CpG-binding protein) gene recently have been reported to cause Rett syndrome (RTT), an X-linked dominant neurodevelopmental disease. We investigated 125 sporadic cases of Rett syndrome by direct sequencing. Thirty different mutations were found in 97 patients with Rett syndrome. Seventee...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Laccone F,Huppke P,Hanefeld F,Meins M

    更新日期:2001-03-01 00:00:00

  • Three novel missense mutations in the glucokinase gene (G80S; E221K; G227C) in Italian subjects with maturity-onset diabetes of the young (MODY). Mutations in brief no. 162. Online.

    abstract::The maturity-onset diabetes of the young (MODY), an autosomal dominant form of non-insulin dependent diabetes mellitus (NIDDM), is caused by mutations in the glucokinase (GK, MODY 2) and in the hepatocyte nuclear factor 1a (MODY 3) and 4a (MODY 1) genes. We have screened the glucokinase gene by the polymerase chain re...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Guazzini B,Gaffi D,Mainieri D,Multari G,Cordera R,Bertolini S,Pozza G,Meschi F,Barbetti F

    更新日期:1998-01-01 00:00:00

  • Understanding the Genomic Structure of Copy-Number Variation of the Low-Affinity Fcγ Receptor Region Allows Confirmation of the Association of FCGR3B Deletion with Rheumatoid Arthritis.

    abstract::Fcγ receptors are a family of cell-surface receptors that are expressed by a host of different innate and adaptive immune cells, and mediate inflammatory responses by binding the Fc portion of immunoglobulin G. In humans, five low-affinity receptors are encoded by the genes FCGR2A, FCGR2B, FCGR2C, FCGR3A, and FCGR3B, ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Rahbari R,Zuccherato LW,Tischler G,Chihota B,Ozturk H,Saleem S,Tarazona-Santos E,Machado LR,Hollox EJ

    更新日期:2017-04-01 00:00:00

  • Mutant NR5A1/SF-1 in patients with disorders of sex development shows defective activation of the SOX9 TESCO enhancer.

    abstract::Nuclear receptor subfamily 5 group A member 1/Steroidogenic factor 1 (NR5A1; SF-1; Ad4BP) mutations cause 46,XY disorders of sex development (DSD), with phenotypes ranging from developmentally mild (e.g., hypospadias) to severe (e.g., complete gonadal dysgenesis). The molecular mechanism underlying this spectrum is un...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sreenivasan R,Ludbrook L,Fisher B,Declosmenil F,Knower KC,Croft B,Bird AD,Ryan J,Bashamboo A,Sinclair AH,Koopman P,McElreavey K,Poulat F,Harley VR

    更新日期:2018-12-01 00:00:00

  • VIPdb, a genetic Variant Impact Predictor Database.

    abstract::Genome sequencing identifies vast number of genetic variants. Predicting these variants' molecular and clinical effects is one of the preeminent challenges in human genetics. Accurate prediction of the impact of genetic variants improves our understanding of how genetic information is conveyed to molecular and cellula...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hu Z,Yu C,Furutsuki M,Andreoletti G,Ly M,Hoskins R,Adhikari AN,Brenner SE

    更新日期:2019-09-01 00:00:00

  • Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose: elucidation of the CARKL gene.

    abstract::The most common mutation in the nephropathic cystinosis (CTNS) gene is a homozygous 57-kb deletion that also includes an adjacent gene carbohydrate kinase-like (CARKL). The latter gene encodes a protein that is predicted to function as a carbohydrate kinase. Cystinosis patients with the common 57-kb deletion had stron...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wamelink MM,Struys EA,Jansen EE,Levtchenko EN,Zijlstra FS,Engelke U,Blom HJ,Jakobs C,Wevers RA

    更新日期:2008-04-01 00:00:00

  • A novel CLCN5 pathogenic mutation supports Dent disease with normal endosomal acidification.

    abstract::Dent disease is an X-linked recessive renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure. Inactivating mutations of CLCN5, the gene encoding the 2Cl- /H+ exchanger ClC-5, have been reported in patients with Dent dis...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bignon Y,Alekov A,Frachon N,Lahuna O,Jean-Baptiste Doh-Egueli C,Deschênes G,Vargas-Poussou R,Lourdel S

    更新日期:2018-08-01 00:00:00

  • Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort.

    abstract::Adams-Oliver syndrome (AOS) is a rare developmental disorder, characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Autosomal dominant forms of AOS are linked to mutations in ARHGAP31, DLL4, NOTCH1 or RBPJ, while DOCK6 and EOGT underlie autosomal recessive inheritance. Data ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Meester JAN,Sukalo M,Schröder KC,Schanze D,Baynam G,Borck G,Bramswig NC,Duman D,Gilbert-Dussardier B,Holder-Espinasse M,Itin P,Johnson DS,Joss S,Koillinen H,McKenzie F,Morton J,Nelle H,Reardon W,Roll C,Salih MA,Sa

    更新日期:2018-09-01 00:00:00

  • Ten novel mutations in the human neurofibromatosis type 1 (NF1) gene in Italian patients.

    abstract::The entire NF1 coding region was analyzed for mutations in a panel of 108 unrelated Italian NF1 patients. Using PTT, SSCP, and DNA sequencing, we found 10 mutations which have never been reported before. Clinical diagnosis of NF1 was established according to the NIH consensus criteria in 100 individuals, while 8 were ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Origone P,De Luca A,Bellini C,Buccino A,Mingarelli R,Costabel S,La Rosa C,Garrè C,Coviello DA,Ajmar F,Dallapiccola B,Bonioli E

    更新日期:2002-07-01 00:00:00

  • Genetic and functional analyses of ZIC3 variants in congenital heart disease.

    abstract::Mutations in zinc-finger in cerebellum 3 (ZIC3) result in heterotaxy or isolated congenital heart disease (CHD). The majority of reported mutations cluster in zinc-finger domains. We previously demonstrated that many of these lead to aberrant ZIC3 subcellular trafficking. A relative paucity of N- and C-terminal mutati...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cowan J,Tariq M,Ware SM

    更新日期:2014-01-01 00:00:00

  • Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.

    abstract::Usher syndrome (USH) is a clinically and genetically heterogeneous autosomal recessive disorder in which sensorineural hearing loss is associated with retinitis pigmentosa. Usher syndrome type 1, the most severe form, is characterized by profound congenital deafness, vestibular dysfunction, and prepubertal onset of re...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Zwaenepoel I,Verpy E,Blanchard S,Meins M,Apfelstedt-Sylla E,Gal A,Petit C

    更新日期:2001-01-01 00:00:00

  • Fluorescent chemical cleavage of mismatches for efficient screening of the factor VIII gene.

    abstract::The detection of mutations in large and complex genes represents a practical challenge in research and diagnostic laboratories. Available methods are either time-consuming or lack sensitivity. Mutation detection in the factor VIII gene, responsible for haemophilia A, is hampered by its large size, its many exons, and ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Freson K,Peerlinck K,Aguirre T,Arnout J,Vermylen J,Cassiman JJ,Matthijs G

    更新日期:1998-01-01 00:00:00

  • Quantitative analysis of SMN1 and SMN2 genes based on DHPLC: a highly efficient and reliable carrier-screening test.

    abstract::Autosomal recessive spinal muscular atrophy (SMA) is a common, fatal neuromuscular disease caused by homozygous absence of the SMN1 gene in approximately 94% of patients. However, a highly homologous SMN2 gene exists in the same chromosome interval, centromeric to SMN1, and hampers detection of SMN1. We present a new,...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Su YN,Hung CC,Li H,Lee CN,Cheng WF,Tsao PN,Chang MC,Yu CL,Hsieh WS,Lin WL,Hsu SM

    更新日期:2005-05-01 00:00:00

  • Characterization of mutations in fifty North American patients with X-linked myotubular myopathy.

    abstract::X-linked myotubular myopathy (MTM1) is a rare developmental disorder of skeletal muscle that is characterized by the presence of abnormal central nuclei in biopsy specimens taken from affected individuals. To date 133 different mutations have been identified in the MTM1 gene worldwide. We report here mutations detecte...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Herman GE,Kopacz K,Zhao W,Mills PL,Metzenberg A,Das S

    更新日期:2002-02-01 00:00:00

  • Novel TSC2 mutations and decreased expression of tuberin in cultured tumor cells with an insertion mutation.

    abstract::Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in many organs. Two genes responsible for TSC, TSC1 and TSC2, were recently identified. TSC1 and TSC2 encode the proteins hamartin and tuberin, respectively, and 337 different mutations have been reported in these genes thus...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Feng JH,Yamamoto T,Nanba E,Ninomiya H,Oka A,Ohno K

    更新日期:2004-04-01 00:00:00

  • Large differences in proportions of harmful and benign amino acid substitutions between proteins and diseases.

    abstract::Genes and proteins are known to have differences in their sensitivity to alterations. Despite numerous sequencing studies, proportions of harmful and harmless substitutions are not known for proteins and groups of proteins. To address this question, we predicted the outcome for all possible single amino acid substitut...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Schaafsma GCP,Vihinen M

    更新日期:2017-07-01 00:00:00

  • SALL4 mutations in Okihiro syndrome (Duane-radial ray syndrome), acro-renal-ocular syndrome, and related disorders.

    abstract::Okihiro/Duane-radial ray syndrome (DRRS) is an autosomal dominant condition characterized by radial ray defects and Duane anomaly (a form of strabismus). Other abnormalities reported in this condition are anal, renal, cardiac, ear, and foot malformations, and hearing loss. The disease is the result of a mutation in th...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Kohlhase J,Chitayat D,Kotzot D,Ceylaner S,Froster UG,Fuchs S,Montgomery T,Rösler B

    更新日期:2005-09-01 00:00:00

  • A rare missense mutation in a type 2 diabetes patient decreases the transcriptional activity of human sterol regulatory element binding protein-1.

    abstract::Sterol regulatory element binding protein 1 (SREBP-1) transcription factors play a key role in energy homeostasis by regulating genes involved in both carbohydrate and lipid metabolism, and in adipocyte differentiation. The 5' end of the mRNA-encoding SREBP-1 exists in two forms, designated 1a and 1c. The divergence r...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Vernia S,Eberlé D,Hernandez Mijares A,Foufelle F,Casado M

    更新日期:2006-02-01 00:00:00

  • Mosaicism for dominant collagen 6 mutations as a cause for intrafamilial phenotypic variability.

    abstract::Collagen 6-related dystrophies and myopathies (COL6-RD) are a group of disorders that form a wide phenotypic spectrum, ranging from severe Ullrich congenital muscular dystrophy, intermediate phenotypes, to the milder Bethlem myopathy. Both inter- and intrafamilial variable expressivity are commonly observed. We presen...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Donkervoort S,Hu Y,Stojkovic T,Voermans NC,Foley AR,Leach ME,Dastgir J,Bolduc V,Cullup T,de Becdelièvre A,Yang L,Su H,Meilleur K,Schindler AB,Kamsteeg EJ,Richard P,Butterfield RJ,Winder TL,Crawford TO,Weiss RB,Mun

    更新日期:2015-01-01 00:00:00

  • Novel mutations in African American patients with glycogen storage disease Type II. Mutations in brief no. 209. Online.

    abstract::The infantile form of GSD II (an inherited deficiency of the lysosomal enzyme, acid alpha-glucosidase, Pompe disease) is a severe and invariably fatal disease characterized by a rapidly progressive generalized hypotonia, hepatomegaly, and cardiomegaly. We have recently demonstrated that African American patients share...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Raben N,Lee E,Lee L,Hirschhorn R,Plotz PH

    更新日期:1999-01-01 00:00:00

  • MEFV mutations in Behçet's disease.

    abstract::Familial Mediterranean fever (FMF) and Behçet's disease (BD), both inflammatory diseases, are highly prevalent in the Middle Eastern and Mediterranean populations. FMF is a Mendelian autosomic recessive disease linked to MEFV, a gene of unknown function. BD in contrast is a polyfactorial disease associated with the ma...

    journal_title:Human mutation

    pub_type: 杂志文章,多中心研究


    authors: Touitou I,Magne X,Molinari N,Navarro A,Quellec AL,Picco P,Seri M,Ozen S,Bakkaloglu A,Karaduman A,Garnier JM,Demaille J,Koné-Paut I

    更新日期:2000-09-01 00:00:00

  • Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history of MYH9-related disease.

    abstract::MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness, presenile cataracts,...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pecci A,Panza E,Pujol-Moix N,Klersy C,Di Bari F,Bozzi V,Gresele P,Lethagen S,Fabris F,Dufour C,Granata A,Doubek M,Pecoraro C,Koivisto PA,Heller PG,Iolascon A,Alvisi P,Schwabe D,De Candia E,Rocca B,Russo U,Rameng

    更新日期:2008-03-01 00:00:00

  • Massive parallel DNA pyrosequencing analysis of the tumor suppressor BRG1/SMARCA4 in lung primary tumors.

    abstract::The tumor suppressor gene, SMARCA4 (or BRG1), which encodes the ATPase component of the chromatin remodeling complex SWI/SNF, is commonly inactivated by mutations and deletions in lung cancer cell lines. However, SMARCA4 alterations appear to be rare in lung primary tumors. Ultra-deep sequencing technologies provide a...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Rodriguez-Nieto S,Cañada A,Pros E,Pinto AI,Torres-Lanzas J,Lopez-Rios F,Sanchez-Verde L,Pisano DG,Sanchez-Cespedes M

    更新日期:2011-02-01 00:00:00