Analysis of polymorphisms flanking the insulin minisatellite

In addition to MVR-PCR studies, a 7.4 kb region representing 3.163 kb 5´ and 4.237 kb 3' of the insulin minisatellite was selected for further analysis. To identify new polymorphisms, 16 individuals were chosen for resequencing based on minisatellite allele structure, in order to maximise lineage diversity within the samples selected. The samples selected, which together represent 21/22 lineages at the minisatellite defined by MVR-PCR, were as follows:

Population   Sample ref.   Minisatellite alleles
Zimbabwe     Z-10          IC35.8     F17.1
Zimbabwe     Z-14          N82.2      U119.1
Zimbabwe     Z-15          Q86.1      X144.1
Zimbabwe     Z-16          T107.1     Y422.1
Zimbabwe     Z-20          G30.1      K44.1
Zimbabwe     Z-21          J43.1      W145.1
Zimbabwe     Z-46          L51.1      K52.2
Zimbabwe     Z-51          IIIB142.2  W148.1
Zimbabwe     Z-58          M86.1      V216.1
Zimbabwe     Z-67          K44.2      Z191.1
Zimbabwe     Z-86          IC31.8     IE39
Kenya        K-3I          H29.1      S110.1
Kenya        K-5B          P79.1      IIIA211.1
UK           UK-101        IC30.1     IIIA159.2
UK           UK-102        ID40.2     ID44.1
UK           UK-103        IIIB144.1  IIIA147.2


Primers used for the resequencing strategy were designed from sequence L15440, published by Lucassen et al. (1993) and are listed on our Primers and ASOs page.

In total, 56 polymorphisms have now been identified within the region studied flanking the insulin minisatellite. The identities and locations of all polymorphisms are shown on our Annotated sequence page.

All 56 polymorphisms were subsequently analysed in 189 African and 189 non-African individuals as follows:

Population         Associated disease          Number of individuals
UK                 None                        102
Kazakhstan         None                         28
Japan              None                         59
Ivory Coast        None                         78
Zimbabwe           None                         69
Kenya              None                         42
Total                                          378


Full genotype data from these individuals can be found on our Genotype data page, with further information on each SNP available at our Allele frequency page. All genotypes were generated by allele-specific oligonucleotide (ASO) hybridisation to nylon membrane dotblots. All ASOs used within this study are presented on our Primers and ASOs page.

To infer haplotypes from our genotype data we employed the PHASE algorithm of Stephens et al. (2001). This algorithm has two key advantages for our purposes. The first is that it can incorporate multi-allelic data and so the minisatellite lineage, as defined by MVR code, could be included within the PHASE input file. The second is that for every heterozygous position in every individual, the probability of the correct determination of haplotype phase is presented. Inferred haplotypes for every individual are listed on our Haplotypes page, with a summary of the data on our Haplotype summary page.

Finally, to determine ancestral states at the polymorphisms considered, the full 7.4 kb region was resequenced in a single chimpanzee, a single gorilla, and a single orangutan. Full sequence information, plus MVR codes generated at the insulin minisatellite, are presented for each species on our Primate data pages.


These pages provide supplementary information for the following publications:

Global haplotype diversity in the human insulin gene region. Stead, J.D.H., Hurles, M.E. and Jeffreys, A.J. Genome Res. 13, 2101-11 (2003)

Structural analysis of insulin minisatellite alleles reveals unusually large differences in diversity between Africans and non-Africans. Stead, J.D.H. and Jeffreys, A.J. Am. J. Hum. Genet. 71, 1273-84 (2002)

Influence of allele lineage on the role of the insulin minisatellite in susceptibility to type 1 diabetes. Stead, J.D.H., Buard, J., Todd, J.A. and Jeffreys, A.J. Hum. Mol. Genet., 9, 2929-2935 (2000).

Allele diversity and germline mutation at the insulin minisatellite. Stead, J.D.H. and Jeffreys, A.J. Hum. Mol. Genet., 9, 713-723 (2000).

If you refer to these data, please cite the relevant publication.




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Last updated: 8 September, 2005
Celia A. May
The views expressed in this document are those of the document owner, John D.H. Stead.