Novel immunoglobulin superfamily gene cluster, mapping to a region of human chromosome 17q25, linked to psoriasis susceptibility

被引:64
作者
Speckman, RA
Daw, JAW
Helms, C
Duan, SH
Cao, L
Taillon-Miller, P
Kwok, PY
Menter, A
Bowcock, AM [1 ]
机构
[1] Washington Univ, Sch Med, Dept Med, Div Dermatol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA
[3] Baylor Univ, Med Ctr, Div Dermatol, Dept Internal Med, Dallas, TX 75246 USA
关键词
D O I
10.1007/s00439-002-0851-y
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Chromosome 17q25 harbors a susceptibility locus for psoriasis (PSORS2). This locus may overlap with loci for atopic dermatitis and rheumatoid arthritis. To further refine the location of PSORS2, we genotyped 242 primarily nuclear families for 15 polymorphic microsatellites mapping to chromosome 17q23-q25. Non-parametric linkage analysis revealed a linkage peak lying close to a novel cluster of genes from the immunoglobulin (Ig) superfamily. This cluster spans >250 kb and harbors five CMRF35-like genes and a sixth inhibitory receptor (CMRF35H) with three ITIM motifs that is transcribed in the opposite direction from the rest. The Ig domains encoded by these genes are most similar to those of the TREM ((t) under bar riggering (r) under bar eceptor (e) under bar xpressed selectively in myeloid cells) molecules, NKp44 and the polymeric immunoglobulin receptor. CMRF35-like genes are only expressed in sub-populations of cells of the myeloid lineage. In order to investigate the association of this region with psoriasis, we genotyped the families for 13 novel microsatellites and 19 SNPs from the region of linkage. A maximum NPL of 1.6 (P = 0.05) was obtained within the interval. Two SNP-based haplotypes revealed some evidence for association with psoriasis. One spanned CMRF35H and includes a non-synonymous polymorphism within CMRF35H (R111Q) (TDT P = 0.03). The second was a three-locus haplotype lying within the first intron of CMRF35A2 (TREM5) (TDT P = 0.04). The novel markers described here will facilitate additional linkage and association studies between the CMRF35 family and disease.
引用
收藏
页码:34 / 41
页数:8
相关论文
共 46 条
[1]   A non-HLA gene within the MHC in psoriasis [J].
Allen, MH ;
Veal, C ;
Faassen, A ;
Powis, SH ;
Vaughan, RW ;
Trembath, RC ;
Barker, JNWN .
LANCET, 1999, 353 (9164) :1589-1590
[2]   A candidate gene for psoriasis near HLA-C, HCR (Pg8), is highly polymorphic with a disease-associated susceptibility allele [J].
Asumalahti, K ;
Laitinen, T ;
Itkonen-Vatjus, R ;
Lokki, ML ;
Suomela, S ;
Snellman, E ;
Saarialho-Kere, U ;
Kere, J .
HUMAN MOLECULAR GENETICS, 2000, 9 (10) :1533-1542
[3]   A locus for paroxysmal kinesigenic dyskinesia maps to human chromosome 16 [J].
Bennett, LB ;
Roach, ES ;
Bowcock, AM .
NEUROLOGY, 2000, 54 (01) :125-130
[4]   Tandem repeats finder: a program to analyze DNA sequences [J].
Benson, G .
NUCLEIC ACIDS RESEARCH, 1999, 27 (02) :573-580
[5]   The genetics of psoriasis: a complex disorder of the skin and immune system [J].
Bhalerao, J ;
Bowcock, AM .
HUMAN MOLECULAR GENETICS, 1998, 7 (10) :1537-1545
[6]   Cutting edge: Inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes [J].
Bouchon, A ;
Dietrich, J ;
Colonna, M .
JOURNAL OF IMMUNOLOGY, 2000, 164 (10) :4991-4995
[7]   Psoriatic arthritis [J].
Brockbank, J ;
Gladman, DD .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2000, 9 (07) :1511-1522
[8]   Prediction of complete gene structures in human genomic DNA [J].
Burge, C ;
Karlin, S .
JOURNAL OF MOLECULAR BIOLOGY, 1997, 268 (01) :78-94
[9]   NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily [J].
Cantoni, C ;
Bottino, C ;
Vitale, M ;
Pessino, A ;
Augugliaro, R ;
Malaspina, A ;
Parolini, S ;
Moretta, L ;
Moretta, A ;
Biassoni, R .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (05) :787-795
[10]   Searching for psoriasis susceptibility genes in Italy: Genome scan and evidence for a new locus on chromosome 1 [J].
Capon, F ;
Novelli, G ;
Semprini, S ;
Clementi, M ;
Nudo, M ;
Vultaggio, P ;
Mazzanti, C ;
Gobello, T ;
Botta, A ;
Fabrizi, G ;
Dallapiccola, B .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1999, 112 (01) :32-35