An analysis of four candidate genes for non-insulin-dependent diabetes using restriction fragment length polymorphism markers
Başlık:
An analysis of four candidate genes for non-insulin-dependent diabetes using restriction fragment length polymorphism markers
Yazar:
Oelbaum, Raymond Stuart, author.
ISBN:
9780438082823
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (262 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Özet:
Non-insulin dependent diabetes mellitus (NIDDM) is characterised by peripheral insulin resistance in muscle, fat and liver cells and by defective insulin secretion from pancreatic beta-cells. Both genetic and environmental factors are thought to be important in the aetiology of NIDDM. The insulin receptor and the three glucose transporters GLUT1, GLUT2 and GLUT4 are prime candidate genes for the inherited defect in NIDDM. The role that these four genes have in causing NIDDM susceptibility was evaluated using a population association approach employing restriction fragment length polymorphism (RFLP) markers at each of these genes. Five RFLP sites at the insulin receptor locus, three GLUT1 RFLPs, four GLUT2 RFLPs and one RFLP site at the GLUT4 locus were analysed in a population of English Caucasian NIDDM subjects and ethnically matched non-diabetic subjects. No allelic association with NIDDM was found on analysing these twelve RFLP loci in English Caucasians. In addition RFLP sites at the GLUT1 locus were analysed in three further populations and no significant allelic association with NIDDM was found. However, there was marked variation in the RFLP allele frequencies at the GLUT1 locus between the different population groups. The frequencies of the XbaI 6.2 kb and BglII 6.2 kb alleles were significantly higher in Blacks compared to English Caucasians (0.51 vs 0.34 and 0.25 vs 0.01 respectively, both p<0.001), as was that of the Stul 3.2 kb allele (0.43 vs 0.33, p<0.05). The frequency of the GLUT1 XbaI 6.2 kb allele was significantly lower in Punjabi Sikhs (0.23) than in English Caucasian and Blacks populations (both p< 0.01), and was also significantly lower in the Welsh Caucasian population (0.26) compared to the English Caucasian (p<0.05) and Black (p< 0.001) populations. Analyses of haplotypes using multiple RFLP sites at the insulin receptor, GLUT1 and GLUT2 genes also showed no haplotype frequency differences between NIDDM and non-diabetic subjects. Tight linkage disequilibrium was found between alleles at the four GLUT2 RFLPs, weak linkage disequilibrium was noted between RFLP alleles at the insulin receptor gene, but no linkage disequilibrium was detected between alleles at three GLUT1 RFLP loci. As obesity is associated with insulin resistance these four genes are also candidate genes for obesity. No allelic association with obesity was seen in either the non-diabetic or NIDDM populations using the 13 RFLP markers above. Similarly there were no significant differences of body mass index between the different genotype groups at each of these RFLP loci in either the non-diabetic or NIDDM populations. These studies suggest that variation at the insulin receptor, GLUT1, GLUT2 or GLUT4 gene does not play a major role in the aetiology of NIDDM. However these studies can not completely eliminate the possibility that mutations at any of these four genes may cause NIDDM in some subjects. These gene loci were amongst the first candidate genes for NIDDM susceptibility to be cloned and it was therefore essential to analyse them in detail for a possible association with NIDDM. The practical limitations in interpreting negative association studies are discussed, as are the relative merits of performing such studies rather than pedigree linkage studies in the genetic analysis of NIDDM. The results presented in this thesis have helped to clarify the genetics of NIDDM, and have directed attention to newer candidate genes.
Notlar:
School code: 1543
Tüzel Kişi Ek Girişi:
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(686846.1) | 686846-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
On Order
Liste seç
Bunu varsayılan liste yap.
Öğeler başarıyla eklendi
Öğeler eklenirken hata oldu. Lütfen tekrar deneyiniz.
:
Select An Item
Data usage warning: You will receive one text message for each title you selected.
Standard text messaging rates apply.