Background: Incidence of type 1 diabetes varies widely around the world, probably due to ethnic differences across populations among other factors.Aims: To determine whether there is an association between disease and ancestry proportions; and to control disease–HLA associations for possible confounding by admixture or population stratification.Subjects and methods: 100 cases and 129 controls participated in the study. Ancestry informative markers, which have considerable differences in frequency between European, West African and Native American populations were used. Type 1 diabetes associated HLA susceptibility/protection alleles were ascertained by PCR using specific primers. Statistical analyses were conducted using STRUCTURE 2.1, ADMIXMAP 3.7, SPSS 16.0 and STRAT 1.0 packages.Results: The results of logistic regression implemented in ADMIXMAP 3.7 indicated that European ancestry was associated with type 1 diabetes mellitus with an odds ratio of 5.7 corresponding to one unit change in European admixture proportion. Association was found between HLA alleles and disease, DQA1*0501, *0301 DQB1*0201 and DRB1*0301, *0401 being susceptibility alleles and DRB1*1501, DQA1*0102/3 and DQB1*0602 being protective alleles.Conclusions: We found an association between European ancestry and type 1 diabetes in our sample, indicating the contribution of ethnicity to incidence differences. Previously reported associations of HLA DR/DQ alleles with disease are confirmed for the admixed Cuban population.

Ancestry-informative marker

10.3109/03014461003766984

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Overview on HLA and DNA typing methods

Biotecnología aplicada (2005)

Annia Ferrer María Elena Fernández Marcelo Nazábal

The term HLA refers to the Human Leukocyte Antigen System, which is controlled by genes on the short arm of chromosome six. The HLA loci are part of the genetic region known as the major histocompatibility complex (MHC). The MHC has genes (including HLA) that form part of the normal function of the immune response. The essential role of the HLA antigens lies in the control of self-recognition and thus defense against microorganisms. The HLA loci, by virtue of their extreme polymorphism ensure that few individuals are identical and thus the population at large is well equipped to deal with attacks. Because some HLA antigens are recognized on all body tissues (rather than just blood cells), the identification of HLA antigens is described as “Tissue typing”. In the last twenty years there has been an exponential growth in the application of DNA technology to the field of Histocompatibility and Immunogenetics. The development and application of several different DNA methods by many laboratories has resulted in that nearly every Histocompatibility and Immunogenetics laboratory performs some DNA typing to detect HLA alleles.

Immunogenetics

Histocompatibility

Tissue typing

HLA-A

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Association of HLA-DRB1, HLA-DQB1 Alleles, and TNF-α Promoter Polymorphisms with Multiple Sclerosis in the Cuban Population

Bionatura journal : (2024)

Alberto Cintado ME Fernández-de-Cossío Marcelo Nazábal T Díaz Mayte Ale

Multiple sclerosis (MS) is an inflammatory, demyelinating, autoimmune disease of the central nervous system. It is known that the Major Histocompatibility Complex class II region produces the most potent effect on MS genetic susceptibility. In addition, the genetic polymorphism within the TNF locus has been involved in the pathogenesis of various autoimmune diseases. This study has the purpose of evaluating HLA-DRB1, HLADQB1 alleles and TNF promotor alpha gene polymorphism (SNP TNF- α -238 G/A; - 243G/A; -308 G/A; - 375 G/A, -856 C/T; -862 C/A) in a sample of Cuban MS patients. Disease-associated HLA susceptibility alleles were genotyped by the SSP-PCR method. The TNF- α genotypes were identified by sequencing. The association was found between HLA and MS, DRB1*15:01, DRB1*14:01, DQA*01:02 and DQB1*06:02 being susceptibility alleles. TNF-α-308 G (OR=1,6, P<0,01) and TNF- α -238 G (OR=2,0, P<0,01) alleles had higher frequency among MS patients than control subjects. The odds ratio was increased among HLADRB1*1501 positive individuals. Our results have shown that the combination of TNF-α-238 G, -308 G with HLA-DRB1*15:01 and HLA-DQA1*01:02 increased susceptibility to MS (p<0.05 OR=4.2) in the Cuban population. Keywords: HLA, TNF-Alpha, polymorphism, SNP, Multiple Sclerosis, Cuban population

Genetic predisposition

SNP

HLA-DRB1

10.21931/bj/2024.02.01.14

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Electrophoretic techniques applied to the detection and analysis of the human microsatellite DG10s478.

Journal of Biomolecular Techniques JBT (2007)

Clara Y Taylor Isabel Guillén Marcelo Nazábal Julio R. Fernández José Antônio Silva

Short nucleotide repetitions (STRs) are commonly used as genetic markers; thus their detection and analysis constitutes a very important tool for the mapping of genetic diseases, as well as for gathering information about genetic polymorphisms at the population level. STRs can be detected with agarose- or acrylamide-based electrophoretic techniques, followed by visualization of the DNA sample with ethidium bromide, silver nitrate, or fluorophore labeling. In this work, we analyzed genomic DNA from five individuals affected with type II diabetes mellitus (T2DM) and five controls (unaffected individuals) in order to know the most precise and reproducible technique for the analysis of the existing polymorphism in the STR DG10S478 of the TCF7L2 gene. The combination of PCR with labeling of the products with the CY5 fluorophore, followed by detection on an ALFexpress sequencer, offered the required resolution to detect the variability in this STR, based solely on size analysis. Our methodology offers similar accuracy and reproducibility at lower costs than existing methods based on the sequencing of PCR products, and is a faster alternative when applied to genotyping studies.

Multiplex

Ethidium bromide

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