Method of determining a genotype by comparing the nucleotide seq

Details Method of determining a genotype by comparing the nucleotide seq Method of determining a genotype by comparing the nucleotide seq

1993-04-14

1998-06-02

Ketter, James

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving nucleic acid

435 912, C12Q 168

Patent

active

057597715

DESCRIPTION:

BRIEF SUMMARY
This application is a continuation of PCT Application Ser. No. PCT/US91/07308 filed Oct. 8, 1991, which is based on Netherlands Application Serial No. 9002259 filed Oct. 17, 1990.


FIELD OF THE INVENTION

The invention relates to a method of determining a genotype by comparing members of a gene family, and also to a kit for tracing genetic variations in a gene family.


BACKGROUND

A gene system is composed of different loci which are in turn composed of one or more genes; these genes may contain variations, so-called different alleles, for each system. The immunoglobulin supergene family, which also includes, inter alia, the T-cell receptor, the immunoglobulin and the HLA (=human leukocyte antigen) gene systems, is characterised by the presence of a large variation (polymorphism). Each of the genes which form part of the gene systems is involved in the immune response in one way or another. Defects in the immune response, which are due to diverse variations in one or more of the gene systems already mentioned, may result in disease.
Genetic variation may thus be associated with diseases or disease symptoms. Identification of loci/alleles may therefore, for example, be of importance in determining the risk of a disease associated with HLA or in detecting variations in the gene system which result in a deviation, and variations for which the latter is not the case. Thus, the HLA-B27 antigen is/are found in 90% of all patients having rheumatoid spondylitis, and HLA-DR3 or HLA-DR4, or both, is/are found in 80% of patients afflicted with insulin-dependent diabetes. Anyone having HLA-B27 has 180 times as such change of getting rheumatodi spondylitis as a person without HLA-B27. Table I (taken from Biotechnologie, een nieuwe industriele revolutie (Biotechnology, A New Industrial Revolution), Antebi, E. and Fishlock, D., published by Natuur en Techniek, Maastricht/Brussels (1987) page 91) shows the most important diseases which are known to be associated with the HLA system. These locus and allele associations may render clinical practice a great service. They are sometimes used for diagnosis and sometimes in the treatment of certain diseases. They furthermore open up the possibility of prevention. It is possible to identify those which have the greatest risk of a particular disease. That is very important in those situations in which preventive or early treatment is possible and the development of the disease can be contained.


TABLE I ______________________________________ The most important diseases associated with the HLA system HLAs Pathology Relative risk* ______________________________________ A1 Hodgkin's disease 1.4 A3 Idiopathic haemochromatosis 8.2 B5 Behcet's disease 6.3 B14, B47 Congenital adrenal hyperplasia 15.4 B27 Rheumatoid spondylitis 87.4 B35 Subacute throiditis 13.7 Cw6 Psoriasis 13.3 DR2 Multiple sclerosis 4.1 DR3 Systemic lupus erythematosus 5.8 DR3 Addison's disease 6.3 DR3 Basedow's disease 3.7 DR3 Myasthenia gravia 2.5 DR3 Extramembranous glomerulopathy 12.0 DR3 and/or DR4 Insulin-dependent diabetes 6.4 DR3 and/or DR7 Coeliac disease 4.8 DR4 Rheumatoid arthritis 4.0 DR4 Pemphigus 14.4 DR5 Biermer's anaemia 5.4 DR5 Hashimoto's disease 5.6 DR5, DRw8 Juvenile arthritis 5.2 ______________________________________ *The relative risk indicates the factor by which the risk of getting a disease is multiplied for people having the HLAs concerned. Individuals having group HLACw6 have, for example, 13.3 times as much chance of getting psoriasis as people not having said antigen.
Genetic variation in the HLA system is furthermore of importance in view of the fact that acceptance in organ and tissue transplants is associated with the presence of the same HLA alleles in the white blood cells, while rejection is related to the presence of various HLA alleles in the white blood cells.
In man the HLA gene family covers a region of 1,500,000 base pairs. This region codes for many genes. Thus, this region contains, in addition to

REFERENCES:
patent: 5045450 (1991-09-01), Thilly et al.
patent: 5066377 (1991-11-01), Rosenbaum et al.
patent: 5110920 (1992-05-01), Erlich
patent: 5192659 (1993-03-01), Simons
patent: 5310893 (1994-05-01), Erlich
Gyllensten et al, Proc. Natl. Acad. Sci, vol.85, Oct. 1988, 7652-56.
McBride L.J., et al., "Automated DNA Sequencing Methods Involving Polymerase Chain Reaction," Clin. Chem. 35(11):2196-2201 (1989).
Parham, P., et al., "Diversity and Diversification of HLA-A.B.C. Alleles," J. Immun. 142(11):3937-3950 (1989).
Scharf, S.J., et al., "Sequence Analysis of the HLA-DR.beta. and HLA-DQ.beta. Loci from Three Pemphigus vulgaris Patients," Human Immunology 22:61-69 (1988).
Tilanus, M.G.J., et al., "A Family with an Apparent HLA DR Triplet: Evidence for Exchange of Functional HLA-DR Beta-Genes between Different Haplotypes," Expl. Clin. Immunogenet 6:162-168 (1989).

Affiliated with

Also associated with

Rating

Method of determining a genotype by comparing the nucleotide seq does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Method of determining a genotype by comparing the nucleotide seq, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of determining a genotype by comparing the nucleotide seq will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1458218