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07627cam a2200445 i 4500 |
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NSK01000222865 |
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HR-ZaNSK |
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20070917165748.0 |
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981020s1997 ci a m 000 0 hrv |
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|9 (HR-ZaNSK)223101
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|9 (HR-ZaNSK)981020001
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|a (HR-ZaNSK)000222865
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|a HR-ZaNSK
|b hrv
|c HR-ZaNSK
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|a ci
|c hr
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|a 575.17(497.5)
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|a Grubić, Zorana
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|a Raspodjela gena razreda II sustava HLA u Hrvatskoj populaciji - molekularna istraživanja :
|b doktorska disertacija /
|c Zorana Grubić.
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|a Zagreb :
|b Z. Grubić,
|c 1997
|e ([s. l. :
|f s. n.])
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|a 143 lista :
|b table, sheme, ilustr., graf. prikazi ;
|c 30 cm.
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|a Doktor prirodnih znanosti - biologija
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|a Mentor: A. Kaštelan
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|a Sveučilište u Zagrebu, Prirodoslovno-matematički fakultet, Zagreb, 1997
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|a Bibliografija: str. 123-135
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|a Summary
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|a Sažetak: U ovoj doktroskoj disertaciji analiziran je polimorfizam alela i haplotipskih veza gena HLA razreda II kod 141 zdravog nesrodnog ispitanika. Osim toga određeni su haplotipovi HLA razreda II na temelju analize 78 obitelji s ukupno 356 članova. Molekularnom metodom PCR-SSO određeni su aleli gena razreda II DRB1, DRB3, DRB5, DQA1, DQB1 i DPB1, i to: 31 alel lokusa DRB1, 4 alela lokusa DRB3, 3 alela lokusa DRB5, 8 alela lokusa DQA1, 13 alela lokusa DQB1 i 17 alela lokusa DPB1. Frekvencija alela HLA razreda II u hrvatskoj populaciji ne pokazuje značajna odstupanja u usporedbi s drugim europskim populacijama. Najčešći aleli na lokusu DRB1 su DRB1*1601, *07, *1501 i *0101. Na lokusu DRB3, koji je naznačen na 45,7% haplotipova, najčešći alel je DRB3*0202 (60.5%), a na lokusu DRB5, koji je naznačen na 22.3% haplotipova, alel DRB5*02(52.4%).
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|a Niti frekvencija alela lokusa DQA1 ne razlikuje se od drugih europskih populacija. Isto vrijedi i za alele lokusa DQB1. Najčešći aleli lokusa DQA1 su DQA1*0102 (25.9%) i *0501 (24.8%), a likusa DQB1 je alel DOB1*0301 (23.5%). Na lokusu DPB1 najčešći alel u hrvatskoj populaciji je alel DPB1*0401 (42.2%). Na temelju dobro poznatoga fenomena neravnoteže udruživanja između slela lokusa HLa razred II istražili smo takpđer 3 dvolokusne (DRB1-DRB3, DRB1-DRB5 i DQA1-DQB1) i trilokusne (DRB1-DQA1-DQB1) haplotipske veze (kombinacija alela). Analiza haplotipskih veza DRB1-DRB3 otkrila je postojanje 13 različitih haplotipskih kombinacija, od kojih su tri netipične (DRB1*0301-DRB3*0202, DRB1*1104-DRB3*0201 i DRB1*1401-DRB3*0201).
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|a Od 8 različitih haplotipskih veza DRB1-DRB5 otkrivene su 3 do sada nepoznate kombinacije Alela i to : DRB1*1501-DRB5*02, DRB1*1502-DRB5*0101 i DRB1*1601-DRB5*0101. Od 52 različite trilokusne haplotipske veze (DRB1-DQA1-DQB1) 24 su tipične (nazočne dva i više puta), a 12 ih je netipičnih. Najčešća trilokusna kombinacija alela je DRB1*1601-DQA1*0102-DQB1**0502 (9.3%). Velika raznolikost haplotipskih veza govori o visokom stupnju varijabilnosti haplotipova HLA razreda II u hrvatskoj populaciji. Obiteljska istarživanja odnose se također na analizu trilokusnih (DRB1- DQA1-DQB1) i četverolokusnih (DRB1-DQA1-DQB1-DPB1) haplotipova i neravnitežu udruživanja alela tih lokusa. Od 78 različitih haplotipova DRB1-DQA1-DQB1, čak 70 se javlja najmanje dvaput.
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|a Tri haplotipa (DRB1*1501-DQA1*0102-DQB1*0502, DRB1*1501-DQA1*0102-DQB1*0604 i DRB1*1301-DQA1*0103-DQB1*0604) otkrivena su po prvi puta. Deset od 77 haplotipova DRB1-DQA-DQB1-DPB1 imaju statistički značenje vrijednosti neravnoteže udruživanja. Niti jedan alel lokusa DPB1 ne pokazuje fenomen isključive povezanosti s ostatkom regije gena razreda II. Najčešći haplotip s najvećom vrijednosti neravnoteže udruživanja u hrvatskoj populaciji je haplotip DRB1*1601-DQA1*0102-DQB1*0502-DPB1*0401 (9.6%;LD=9.3). Nije otkriven niti jedan crossing-over između lokusa DRB1, DQA1 i DQB1. Jedan crossing-over otkriven je samo između lokusa DQB1 i DPB1, što je u skladu s očekivanim brojem rekombinacija između ovih lokusa (0.8[plus minus]0.4%).
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|a Summary:In this studiy the HLA-class II alleles and haplotypic associations have been studied in a population of 141 unrelated healthy Croatians, while HLA class II haplotype analysis is provided in 78 families with 356 members. All subjects were tested for HLA class II loci (DRB1, DRB3, DRB5, DQA1, DQB1 and DPB1) using PCR-SSO method. Thirty one DRB1, 4 DRB3, 3 DRB5, 8 DQA1, 13 DQB1 and 17 DPB1 alleles were found in the tested population. The frequency of HLA class II alleles in Croatians did not reveal any significant differences compared with other European populations. DRB1*1601, *07, *1501 and *0101 are the most frequent alleles at DRB1 locus. At DRB3 locus (presents at 45.7% chromosome) the most frequent allele is DRB3*0202 (60.5%), while the most frequent at DRB5 locus (presents at 22.3% chromosomes) is DBR5*02 (52.4%).
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|a At the DQA1 locus two alleles predominate: DQA1*0102 (25.9%) and *0501 (24.8%), while the most frequent DQB1 allele is *0301 (23.5%). Analysis of DPB1polymorphism showed, as in other Europeans, that DPB1*0401 (42.2%) is the most frequent allele. Three different two locus haplotypic associations (DRB1-DRB3, DRB1-DRB5 and DQA1-DQB1) as well as one three locus (DRB1-DQA1-DQB1) haplotypic associations were assigned on the basis of well known linkage disequlibrium. Among 13 different DRB1-DRB3 haplotypic associations in Croatians, three unusual DRB1-DRB3 associations have been observed (DRB1*0301-DRB3*0202, DRB1*1104-DRB3*0201 and DRB1*1401-DRB3*0201). Further, three new unusual DRB1-DRB5 associations were found: DRB1*1501-DRB5*02, DRB1*1502-DRB5*0101 and DRB1*1601-DRB5*0101, whichhave been reported before.
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|a Among 118 unrelated individuals, 52 different DRB1-DQA1-DQB1 haplotypic associations were observed. Twenty-four probable haplotypes were foundmore than two times, while twelve associations were unusual. The most frequen was: DRB1*1601-DQA1*0102-DQB1*0502 (9.3%). That large number of haplotypic associations, suggest that main characteristic of Croatian populations is a great heterogeneity of HLA class II haplotypes. In family study, three (DRB1-DQA1-DQB1) and four (DRB1-DQA1-DQB1-DPB1)haplotype analiyses as well as linkage disequlibrium were performed. Among 78 distinct haplotypes, 70 haplotypes were observed two or more times, three of them (DRB1*1501-DQA1*0102-DQB1*0502, DRB1*1501-DQA1*0102-DQB1*0604 and DRB1*1301-DQA1*0103-DQB1*0604) are new (not reported before).
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|a Thirteen different DRB1-DQA1-DQB1 haplotypes showed statistically significant value of linkage disqulibrium, while haplotaype DRB1*1601-DQA1*0102-DQB1*0502 showed the highest linkage disequlibrium (LD=10.3). Among 77 distinct DRB1-DQA1-DQB1-DPB1 haplotypes for ten combinations of DRB1-DQA1-DQB1-DPB1 alleles a statistically significant linkage disequlibrium was observed. The most frequent haplotype with highest LD in Croatians is DRB1*1601-DQA1*0102-DQB1*0502-DPB1*0401 (9.6%;LD=9.3). In family study no crossing-over were found between DRB1 and DPB1, DQA1 and DQB1 loci. Howevwer one crossing-over was detected between DQB1 nad DPB1 loci, resulting in an estimated percentage of recombinations (0.8[plus minus]0.4%).
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| 650 |
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|a Genetika populacije
|z Hrvatska
|2 nskps
|
| 700 |
1 |
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|a Kaštelan, Andrija
|4 cns
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| 981 |
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|p CRO
|r HRB1997
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| 998 |
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|n DCD/97
|c sbno9901
|c dkrp9904
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| 852 |
4 |
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|j DCD-ZG-77/98
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| 876 |
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|e DCD
|a 77/1998
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| 886 |
0 |
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|2 unimarc
|b 07346iam0 2200373 450
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