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M Kamio,
A Meguro,
M Ota,
N Nomura,
K Kashiwagi,
F Mabuchi,
H Iijima,
K Kawase,
T Yamamoto,
M Nakamura, [......],
T Fukuchi,
H Abe,
T Higashide,
K Sugiyama,
T Kanamoto,
Y Kiuchi,
A Iwase,
S Ohno,
H Inoko, N Mizuki
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ABSTRACT: To investigate whether the GLC3A locus harboring the CYP1B1 gene is associated with normal tension glaucoma (NTG) in Japanese patients.
One hundred forty-two Japanese patients with NTG and 101 Japanese healthy controls were recruited. Patients exhibiting a comparatively early onset were selected as this suggests that genetic factors may show stronger involvement. Genotyping and assessment of allelic diversity was performed on 13 highly polymorphic microsatellite markers in and around the GLC3A locus.
There were decreased frequencies of the 444 allele of D2S0416i and the 258 allele of D2S0425i in cases compared to controls (P = 0.022 and P = 0.034, respectively). However, this statistical significance disappeared when corrected (Pc > 0.05). We did not find any significant association between the remaining 11 microsatellite markers, including D2S177, which may be associated with CYP1B1, and NTG (P > 0.05).
Our study showed no association between the GLCA3 locus and NTG, suggesting that the CYP1B1 gene, which is reportedly involved in a range of glaucoma phenotypes, may not be an associated factor in the pathogenesis of NTG.
Clinical ophthalmology (Auckland, N.Z.) 02/2009; 3:183-8.
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M Akiyama,
K Yatsu,
M Ota,
Y Katsuyama,
K Kashiwagi,
F Mabuchi,
H Iijima,
K Kawase,
T Yamamoto,
M Nakamura,
A Negi,
T Sagara,
N Kumagai,
T Nishida,
M Inatani,
H Tanihara,
S Ohno,
H Inoko, N Mizuki
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to investigate the association between normal tension glaucoma and the candidate disease locus glaucoma 1, open angle, B (GLC1B) on chromosome 2. There are many reports describing the results of association or linkage studies for primary open angle glaucoma (POAG), with GLC1B as one of the loci associated with normal or moderately elevated intraocular pressure. However, there are few reports about the association of genes or defined genomic regions with normal tension glaucoma, which is the leading type of glaucoma in Japan. The GLC1B locus is hypothesized to be a causative region for normal tension glaucoma.
Genomic DNA was extracted from whole blood of normal tension glaucoma (n = 143) and healthy controls (n = 103) of Japanese origin.
Fifteen microsatellite markers within and/or near to the GLC1B locus were genotyped, and their association with normal tension glaucoma was analysed. Two markers D2S2264 and D2S176 had significant positive associations.
The D2S176 marker had the strongest significant association and it is located 24 kb from the nearest gene NCK2, which now becomes an important new candidate gene for future studies of its association with normal tension glaucoma.
The British journal of ophthalmology 10/2008; 92(9):1293-6. · 2.92 Impact Factor
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Y Takemoto,
T Naruse,
K Namba,
N Kitaichi,
M Ota,
Y Shindo, N Mizuki,
A Gul,
W Madanat,
H Chams,
F Davatchi,
H Inoko,
S Ohno,
A Kimura
[show abstract]
[hide abstract]
ABSTRACT: Behçet's disease (BD) is a chronic inflammatory disease characterized by oral aphthous ulcers, genital ulcers, uveitis and skin lesions. Etiology and pathogenesis of BD are not fully elucidated, but the association with human leukocyte antigen (HLA)-B51 or B*5101 has been repeatedly reported. Previous studies have shown that there are few sequence variations in the protein-coding region of B51, while there is a report on many variations in the 5'-flanking region and intron. In this study, HLA-B*5101 gene from 37 individuals including Japanese, Turkish, Jordanian and Iranian patients and healthy controls were fully sequenced to further clarify the B*5101 gene in association with BD. We found that all the patients and healthy controls carried B*510101 with no variation in the 5'-flanking region, exon and intron. However, seven polymorphisms were found in the 3'-flanking region. These polymorphisms composed of six haplotypes that were shared and stretched over the ethnic groups, suggesting that the susceptibility to BD was conferred by the B*510101 itself and not by any genes in linkage disequilibrium with B*510101. In addition, phylogenetic analyses of B*510101 showed that the 3'-flanking sequences followed an evolutional divergence differently from that of the other regions, implying that a unifying selection might operate to conserve B*510101.
Tissue Antigens 09/2008; 72(4):347-53. · 2.59 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: To ascertain and define the position of a potential disease susceptibility gene around D21S0083i prioritized during our previous whole genome case-control association analysis with 27,158 microsatellite markers, in Japanese high-myopia patients.
520 high myopic patients and 520 healthy controls were genotyped using 39 SNPs distributed around D21S0083i on chromosome 21q22.3.
Only 1 SNP (rs2839471) of 39 SNPs was significant after correction for multiple testing (allele T: P=0.00027, Pc=0.01, OR=1.684). The SNP (rs2839471) did not reside in haplotype blocks constructed by the pair-wise linkage disequilibrium between the SNPs.
The SNP (rs2839471) is suggested to be located in the frequent recombinant region within UMODL1. Together this region might play a critical role for susceptibility to high myopia, and warrants further confirming studies and investigations as to the mechanisms by which UMODL1 may contribute to myopia.
Eye (London, England) 07/2008; 23(1):222-9. · 1.97 Impact Factor
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M Akahoshi,
M Ishihara,
K Namba,
N Kitaichi,
Y Ando,
S Takenaka,
T Ishida,
S Ohno, N Mizuki,
H Nakashima,
T Shirakawa
[show abstract]
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ABSTRACT: CARD15 was first identified as a susceptibility gene for Crohn's disease. More recently, CARD15 mutations were shown to be associated with the pediatric granulomatous inflammatory diseases, Blau syndrome and early-onset sarcoidosis (EOS). The aim of the present study was to evaluate whether CARD15 variants also play a role in patients with ordinary sarcoidosis other than EOS. We enrolled 135 Japanese sarcoidosis patients with uveitis as well as 95 healthy individuals and performed mutation analysis by direct sequencing of CARD15 exon 4. Direct DNA sequencing in the sarcoidosis patients showed eight CARD15 variants, including five novel mutations (13402C>T, 13543C>T, 13775C>A, 13937G>A, and 14079C>T). Compared with healthy individuals, CARD15 mutations are not common in the Japanese patients with sarcoidosis. Based on the results, we examined the clinical manifestations in patients with sarcoidosis according to their CARD15 mutations. Sarcoidosis patients with these mutations have no specific clinical features with regard to course of the disease or disease severity. Our results indicate that in general, CARD15 mutations may not contribute to the risk of sarcoidosis.
Tissue Antigens 07/2008; 71(6):564-7. · 2.59 Impact Factor
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Annals of the rheumatic diseases 06/2008; 67(5):725-7. · 8.11 Impact Factor
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ABSTRACT: This paper describes a case of vertical distraction osteogenesis of a free vascularized osteocutaneous scapular flap in the reconstructed mandible before implant therapy. The patient was a 67-year-old woman with squamous cell carcinoma of the right lower gingiva. She underwent segmental mandibulectomy for tumor ablation and reconstruction with an osteocutaneous scapular flap. The distraction protocol, clinical course and implant therapy are presented. Through this procedure, the bone height of the scapular graft increased by 10mm. Implants with adequate length could be placed in the distracted area. Two years after masticatory loading, the condition of these implants was stable. Vertical distraction osteogenesis of the scapular flap was considered effective when performed before implant therapy, to facilitate postoperative functional and esthetic restoration after tumor resection.
International Journal of Oral and Maxillofacial Surgery 06/2008; 37(5):481-3. · 1.51 Impact Factor
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ABSTRACT: Toll-like receptors (TLRs) play an important role in the induction of defense mechanisms of the innate and adaptive immune responses to microbial pathogens. Genetic polymorphisms within the TLR9 gene have been reported to be associated with a variety of inflammatory and infectious diseases. Behçet's disease (BD) is a chronic inflammatory disease, and the etiology of BD has yet to be fully elucidated. We investigated the potential association of the TLR9 gene with susceptibility to BD by analyzing the frequency of nine single nucleotide polymorphisms (SNPs) in a population of 200 Japanese BD patients and 102 randomized controls. Our results showed that SNPs in the TLR9 gene were not significantly associated with susceptibility to BD.
Tissue Antigens 12/2007; 70(5):423-6. · 2.59 Impact Factor
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ABSTRACT: Toll-like receptors (TLRs) play an important role in the induction of defense mechanisms of the innate and adaptive immune responses to microbial pathogens. Genetic polymorphisms within the TLR9 gene have been reported to be associated with a variety of inflammatory and infectious diseases. Behçet’s disease (BD) is a chronic inflammatory disease, and the etiology of BD has yet to be fully elucidated. We investigated the potential association of the TLR9 gene with susceptibility to BD by analyzing the frequency of nine single nucleotide polymorphisms (SNPs) in a population of 200 Japanese BD patients and 102 randomized controls. Our results showed that SNPs in the TLR9 gene were not significantly associated with susceptibility to BD.
Tissue Antigens 10/2007; 70(5):423 - 426. · 2.59 Impact Factor
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ABSTRACT: The present study represents the first four-digit allele genotyping of HLA-A and -B in Japanese Behcet's disease (BD) patients and controls using a new genotyping method (named the PCR-SSOP-Luminex method) to determine the association of certain HLA-A or -B alleles with BD. Peripheral blood lymphocytes were collected from 180 Japanese BD patients and 170 healthy controls. The genotype frequency of HLA-B*5101 was significantly increased in the patients (61.7%) as compared with the controls (15.9%) (Pc = 1 x 10(-16), OR = 8.5). When we recalculated the phenotype frequencies after excluding the HLA-B*51-positive patients and controls to account for the effects of the linkage disequilibrium and the abundance of the HLA-B*51 allele, the frequencies of HLA-A*2602 and HLA-B*3901 had a weak association in the patient group without HLA-B*51 as compared with the control group without HLA-B*51 (A*2602; Pc = 0.130, OR = 4.3, B*3901; Pc = 0.099, OR = 3.5). This study confirmed on the basis of using a new and more accurate genotyping method that Japanese BD patients have a strong primary association with HLA-B*5101. The significant increase of HLA-A*2602 and B*3901 in the patient group without HLA-B*51 suggests that these two alleles might also have some secondary influence on the onset of BD.
Tissue Antigens 06/2006; 67(5):390-4. · 2.59 Impact Factor
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E Nomura,
M Sato,
H Suemizu,
T Watanabe,
T Kimura,
K Yabuki,
K Goto,
N Ito,
S Bahram,
H Inoko, N Mizuki,
S Ohno,
M Kimura
[show abstract]
[hide abstract]
ABSTRACT: Major histocompatibility complex (MHC) class I chain-related gene A and B (MICA and MICB) are located very close to HLA-B. MICA is reported to be strongly associated with Behçet's disease (BD), a multisysytemic inflammation disorder characterized by oral apthous ulcers, skin lesions and genital ulcers. These two molecules are highly conserved at the amino acid levels. To determine the function of MICB in vivo and the relationship between the expression of MICB and BD experimentally, we produced several transgenic mouse lines (termed CAG-MICB) expressing human MICB cDNA under a ubiquitous promoter. They exhibited a 50% increase in the number of white blood cells compared with their non-transgenic littermates, and also exhibited a 10-20% reduction in body weight compared with non-transgenic littermates. Exfoliation of the skin first appeared around 7 days after birth and disappeared after 2 weeks of age. This was repeatedly observed in the transgenic offspring of two independent CAG-MICB lines examined. Histopathological analysis of skin of young mice exhibiting skin abnormalities revealed hyperkeratosis of the epidermis and thickening of the granular layer with slight infiltration of inflammatory cells in the dermis without any vasculitis. Other remarkable abnormalities associated with BD have not been observed in the CAG-MICB lines. Furthermore, fluorescein angiography of eyes of the CAG-MICB lines was performed, but there were no marked changes of BD-related uveitis in the ocular fundus. These findings suggest that (i) MICB expression is related to temporary skin inflammation, and (ii) expression of MICB is not directly associated with BD.
Tissue Antigens 05/2003; 61(4):300-7. · 2.59 Impact Factor
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N Mizuki,
K Yabuki,
M Ota,
Y Katsuyama,
H Ando,
E Nomura,
K Funakoshi,
F Davatchi,
H Chams,
B Nikbin,
A A Ghaderi,
S Ohno,
H Inoko
[show abstract]
[hide abstract]
ABSTRACT: We have previously suggested that in a Japanese population the susceptible locus for Behçet's disease (BD) is HLA-B51 itself. To confirm this finding in another population, we performed HLA class I typing using the PCR-SSP method and analyzed eight polymorphic markers distributed within 1100 kb around the HLA-B gene using automated sequencer and subsequent automated fragment detection by fluorescent-based technology with the DNA samples of 84 Iranian patients with BD and 87 healthy ethnically matched controls. As a result, three microsatellite alleles (MICA-A6, MIB-348, C1-4-1-217) and HLA-B51 were found to be strongly associated with BD. Of these alleles HLA-B51 is the most strongly associated allele. There were no alleles that were increased in allele frequency at any microsatellite loci centromeric of MICA or telomeric of HLA-B51. Therefore, HLA-B51 was confirmed to be by far the most strongly associated gene with BD in an Iranian population.
Tissue Antigens 12/2002; 60(5):396-9. · 2.59 Impact Factor
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N Mizuki,
M Ota,
Y Katsuyama,
K Yabuki,
H Ando,
T Shiina,
G D Palimeris,
E Kaklamani,
D Ito,
S Ohno,
Hidetoshi Inoko
[show abstract]
[hide abstract]
ABSTRACT: Behçet's disease (BD) is widely known to be strongly associated with human leukocyte antigen (HLA) B51 in many different ethnic groups.Recently, HLA-B51 allele typing of Greek BD patients was performed to study the distribution of B*5101-B*5107 alleles in this Greek population, the B51 antigen strongly associated with BD was found to be predominantly encoded by allele B*5101. As it is now known that the B51 antigen can be encoded by 21 alleles, B*5101-B*5121, we performed HLA-B*51 allele genotyping among 58 Greek patients with BD. After serological HLA typing, typing of HLA-B*51 alleles was performed using the polymerase chain reaction-sequencing-based typing (PCR-SBT) method. The frequency of the B51 antigen was found to be significantly higher in the patient group as compared with the control group (75.9% of patients vs 22.0% of controls. In the genotyping of B51 alleles, 34 out of 44 B51-positive patients possessed B*5101, 13 out of the 44 carried B*5108. In contrast, all of the 9 B51-positive normal controls carried B*5101. This study revealed a strong association between Greeks with BD, both B*5101, B*5108, provided important insights into the molecular mechanism underlying the association between HLA status, this disease.
Tissue Antigens 03/2002; 59(2):118-21. · 2.59 Impact Factor
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S.S. Seki,
K. Sugimura,
M. Ota,
J. Matsuzawa,
Y. Katsuyama,
K. Ishizuka,
T. Mochizuki,
K. Suzuki,
O. Yoneyama, N. Mizuki,
T. Honma,
H. Inoko,
H. Asakura
[show abstract]
[hide abstract]
ABSTRACT: We previously reported a conserved haplotype of HLA B52-DR2 and a significantly high frequency of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) transmembrane-short tandem repeat (TM-STR) 6 allele in Japanese patients with ulcerative colitis (UC). To examine the predominance of the MICA TM-STR 6 allele as a marker of the susceptibility to UC within the susceptible haplotype, the association of each allele with UC was estimated following stratification of the patients to control for any possible confounding effects of other alleles positively associated with UC. Sixty-four patients with UC and 236 unrelated healthy controls were included in this study. All subjects were Japanese. HLA-A, -B, -C, and -DR antigens were determined serologically. A triplet repeat polymorphism of the MICA was determined by direct sequencing. To control for the effect of linkage disequilibrium, Mantel-Haenszel weighed odds ratios were calculated. Significantly higher phenotype frequencies of B52, MICA TM-STR 6, and DR2 were observed in patients with UC. Linkage disequilibria among alleles associated with UC revealed that a B52 –MICA TM-STR 6 – DR2 haplotype was conserved in patients with UC, as in controls. When the association of HLA-B52 was estimated after patient stratification for the possible confounding effect of MICA TM-STR 6 or DR2, a strong significant association of B52 with UC was still observed. In contrast, no association with UC was observed for MICA TM-STR 6 or DR2, after stratification of the possible confounding effect of HLA-B52. These results imply that the significant increase in MICA TM-STR 6 in Japanese patients with UC is attributable to linkage disequilibrium with HLA-B52.
Tissue Antigens 12/2001; 58(2):71 - 76. · 2.59 Impact Factor
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ABSTRACT: To clarify the prevalence of open-angle glaucoma (OAG) and its relationship to refraction among a Japanese population with a broad range of ages including children and adolescents, an 1-year epidemiological survey was conducted. The subjects of this study were 64,394 asymptomatic individuals who had attended the glasses and contact lens center in Yokohama, Japan from February 15, 1999 to February 14, 2000 and had been subjected to several optical examinations. The results of this study showed that the overall prevalence of OAG was 1.19% (1.14% for men, and 0.98% for women). Prevalence for children aged 6 to 14 of both sexes was approximately 0.5%. There were significant positive associations between the strength (diopter) of myopic refraction and OAG prevalence among all the examined subjects.
Journal of Clinical Epidemiology 12/2001; 54(11):1151-8. · 4.27 Impact Factor
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[show abstract]
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ABSTRACT: Behçet's disease (BD) is known to be associated with human leukocyte antigen (HLA) B51 in many different ethnic groups. An increased incidence of HLA-B51 in the patient group has also been reported in a Japanese population. Recently, the B51 antigen has been identified to comprise 21 alleles, B*5101-B*5121. Further, not only HLA-B*5101 but also HLA-B*5108 were found to be relatively increased in the patient groups among Italian and Saudi Arabian populations. Therefore, we performed HLA-B*51 allele genotyping by the polymerase chain reaction-sequencing based typing (PCR-SBT) method in order to investigate whether there is any correlation of one particular B51-associated allele with Japanese BD. Ninety-six Japanese patients with BD and 132 healthy Japanese volunteers were enrolled in this study. As a result, the phenotype frequency of the B51 antigen was confirmed to be remarkably increased in the patient group as compared to the ethnically matched control group (59.4% in patients vs. 13.6% in controls; Pc=0.0000000000098, R.R.=9.3). In the B*51 allele genotyping, 56 out of 57 B51-positive patients were defined as B*5101 and the remaining one was B*5102. In contrast, all of 18 B51-positive normal controls were B*5101. None of the Japanese patients and healthy controls carried the HLA-B*5108 allele. This study revealed that B*51 allelic distribution in Japanese was different from those in Italian and Saudi Arabian populations, and that the significantly high incidence of the HLA-B51 antigen in the Japanese BD patient group was mostly caused by the significant increase of the HLA-B*5101 allele.
Tissue Antigens 10/2001; 58(3):181-4. · 2.59 Impact Factor
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[show abstract]
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ABSTRACT: Behçet's disease is known to be associated with HLA-B51 in many different populations. Genetic evidence supports that the susceptible gene for Behçet's disease is the HLA-B51 allele at the HLA-B locus. This study was aimed to determine the HLA-B51 nucleotide sequence variation in three Behçet's disease patients and three healthy controls in order to elucidate if any disease specific mutations or polymorphisms may exist in the HLA-B51 gene of patients. Long-range polymerase chain reaction (PCR) was first carried out to give a PCR-amplified product of 9.5 kb which was then used as a template for nested PCR to give a final amplified product of 4.2 kb. This final product containing the 1.3-kb promoter/enhancer region and the entire HLA-B gene except for a 363-bp 3' terminal end segment encoding the 3' untranslated region was subcloned by the BP cloning technique and sequenced. The sequencing results showed that all the patients possessed the HLA-B*51011 allele, and there were no differences in the exonic nucleotide sequences between the three Behçet's disease patients and the three healthy controls. The HLA-B*51011 intronic and promoter/enhancer nucleotide sequences from the three patients had 22 single nucleotide polymorphisms (SNPs), a single insertion of 6 bp and a single deletion of 2 bp. On the other hand, the three healthy controls had 24 SNPs in their intronic and promoter/enhancer regions. However, none of these polymorphisms in the patients were specific for the disease. Therefore, these results clearly demonstrate that the HLA-B exonic sequence that encodes the HLA-B51 allele is the real pathogenic factor in Behçet's disease.
Tissue Antigens 09/2001; 58(2):77-82. · 2.59 Impact Factor
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S S Seki,
K Sugimura,
M Ota,
J Matsuzawa,
Y Katsuyama,
K Ishizuka,
T Mochizuki,
K Suzuki,
O Yoneyama, N Mizuki,
T Honma,
H Inoko,
H Asakura
[show abstract]
[hide abstract]
ABSTRACT: We previously reported a conserved haplotype of HLA B52-DR2 and a significantly high frequency of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) transmembrane-short tandem repeat (TM-STR) 6 allele in Japanese patients with ulcerative colitis (UC). To examine the predominance of the MICA TM-STR 6 allele as a marker of the susceptibility to UC within the susceptible haplotype, the association of each allele with UC was estimated following stratification of the patients to control for any possible confounding effects of other alleles positively associated with UC. Sixty-four patients with UC and 236 unrelated healthy controls were included in this study. All subjects were Japanese. HLA-A, -B, -C, and -DR antigens were determined serologically. A triplet repeat polymorphism of the MICA was determined by direct sequencing. To control for the effect of linkage disequilibrium, Mantel-Haenszel weighed odds ratios were calculated. Significantly higher phenotype frequencies of B52, MICA TM-STR 6, and DR2 were observed in patients with UC. Linkage disequilibria among alleles associated with UC revealed that a B52 - MICA TM-STR 6 - DR2 haplotype was conserved in patients with UC, as in controls. When the association of HLA-B52 was estimated after patient stratification for the possible confounding effect of MICA TM-STR 6 or DR2, a strong significant association of B52 with UC was still observed. In contrast, no association with UC was observed for MICA TM-STR 6 or DR2, after stratification of the possible confounding effect of HLA-B52. These results imply that the significant increase in MICA TM-STR 6 in Japanese patients with UC is attributable to linkage disequilibrium with HLA-B52.
Tissue Antigens 09/2001; 58(2):71-6. · 2.59 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Behçet’s disease (BD) is known to be associated with human leukocyte antigen (HLA) B51 in many different ethnic groups. An increased incidence of HLA-B51 in the patient group has also been reported in a Japanese population. Recently, the B51 antigen has been identified to comprise 21 alleles, B*5101–B*5121. Further, not only HLA-B*5101 but also HLA-B*5108 were found to be relatively increased in the patient groups among Italian and Saudi Arabian populations. Therefore, we performed HLA-B*51 allele genotyping by the polymerase chain reaction-sequencing based typing (PCR-SBT) method in order to investigate whether there is any correlation of one particular B51-associated allele with Japanese BD. Ninety-six Japanese patients with BD and 132 healthy Japanese volunteers were enrolled in this study. As a result, the phenotype frequency of the B51 antigen was confirmed to be remarkably increased in the patient group as compared to the ethnically matched control group (59.4% in patients vs. 13.6% in controls; Pc=0.0000000000098, R.R.=9.3). In the B*51 allele genotyping, 56 out of 57 B51-positive patients were defined as B*5101 and the remaining one was B*5102. In contrast, all of 18 B51-positive normal controls were B*5101. None of the Japanese patients and healthy controls carried the HLA-B*5108 allele. This study revealed that B*51 allelic distribution in Japanese was different from those in Italian and Saudi Arabian populations, and that the significantly high incidence of the HLA-B51 antigen in the Japanese BD patient group was mostly caused by the significant increase of the HLA-B*5101 allele.
Tissue Antigens 08/2001; 58(3):181 - 184. · 2.59 Impact Factor
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T Shiina,
A Ando,
Y Suto,
F Kasai,
A Shigenari,
N Takishima,
E Kikkawa,
K Iwata,
Y Kuwano,
Y Kitamura, [......],
H Tashiro,
G Tamiya,
A Kohda,
K Okumura,
T Ikemura,
E Soeda, N Mizuki,
M Kimura,
S Bahram,
H Inoko
[show abstract]
[hide abstract]
ABSTRACT: Human chromosomes 1q21-q25, 6p21.3-22.2, 9q33-q34, and 19p13.1-p13.4 carry clusters of paralogous loci, to date best defined by the flagship 6p MHC region. They have presumably been created by two rounds of large-scale genomic duplications around the time of vertebrate emergence. Phylogenetically, the 1q21-25 region seems most closely related to the 6p21.3 MHC region, as it is only the MHC paralogous region that includes bona fide MHC class I genes, the CD1 and MR1 loci. Here, to clarify the genomic structure of this model MHC paralogous region as well as to gain insight into the evolutionary dynamics of the entire quadriplication process, a detailed analysis of a critical 1.7 megabase (Mb) region was performed. To this end, a composite, deep, YAC, BAC, and PAC contig encompassing all five CD1 genes and linking the centromeric +P5 locus to the telomeric KRTC7 locus was constructed. Within this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed. This led to the mapping of a total of 41 genes (12 expressed genes, 12 possibly expressed genes, and 17 pseudogenes), among which 31 were novel. The latter include 20 olfactory receptor (OR) genes, 9 of which are potentially expressed. Importantly, CD1, SPTA1, OR, and FCERIA belong to multigene families, which have paralogues in the other three regions. Furthermore, it is noteworthy that 12 of the 13 expressed genes in the 1q21-q22 region around the CD1 loci are immunologically relevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI-16, AIM2, BL1A, FY and FCERIA. This functional convergence of structurally unrelated genes is reminiscent of the 6p MHC region, and perhaps represents the emergence of yet another antigen presentation gene cluster, in this case dedicated to lipid/glycolipid antigens rather than antigen-derived peptides.
Genome Research 06/2001; 11(5):789-802. · 13.61 Impact Factor
