scholarly journals Next Generation Sequencing Identifies the HLA-DQA1*03:03 Allele in the Type 1 Diabetes Risk-Associated HLA-DQ8 Serotype

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1879
Author(s):  
Jürgen Enczmann ◽  
Vera Balz ◽  
Maximilian Hoffmann ◽  
Sebastian Kummer ◽  
Christina Reinauer ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Next Generation Sequencing ◽  
Hla Class Ii ◽  
Diabetes Risk ◽  
Next Generation ◽  
Exon 2 ◽  
Hla Genotyping ◽  
Hla Dqa1 ◽  
Generation Sequencing

The highest genetic type 1 diabetes risk is conferred by HLA class II haplotypes defined by alleles at the HLA-DR and -DQ loci. The combination of HLA-DQA1*03:01 and DQB1*03:02 alleles (summarized as ‘HLA-DQ8′) is reported to be among the two most prevalent HLA class II haplotypes in Caucasian type 1 diabetes patients. This classification is based on conventional genotyping of exon 2 of the DQ gene locus and excludes exon 3. In this study, HLA genotyping on the type 1 diabetes susceptibility loci HLA-DRB1, DQA1 and DQB1 was performed using a high-resolution next generation sequencing method. In addition to the routinely examined exon 2, exon 3 was also sequenced. Samples from 229 children with type 1 diabetes were included and compared to a cohort of 9,786 controls. In addition to previously described HLA-DQ haplotypes in type 1 diabetes patients, we found that as well as HLA-DQA1*03:01,HLA-DQA1*03:03 also contributed to HLA-DQ8. HLA-DQA1*03:03 differs from HLA-DQA1*03:01 by one nucleotide substitution in exon 3 at position 160, leading to a single amino acid replacement. DRB1*04:05 was exclusively associated with DQA1*03:03 whereas the DRB1*04:01 haplotype comprised either DQA1*03:01 or DQA1*03:03. Significantly increased type 1 diabetes risk was confirmed for all these haplotypes with only minor differences between DQA1*03:01 and DQA1*03:03 alleles. This study identified the HLA-DQA1*03:03 allele as an addition to the already known type 1 diabetes risk haplotypes, and can contribute to more precise HLA genotyping approaches.

scholarly journals Next-Generation Sequencing Reveals ThatHLA-DRB3,-DRB4, and-DRB5May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes

Diabetes ◽  
2016 ◽  
Vol 65 (3) ◽  
pp. 710-718 ◽  
Author(s):  
Lue Ping Zhao ◽  
Shehab Alshiekh ◽  
Michael Zhao ◽  
Annelie Carlsson ◽  
Helena Elding Larsson ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Next Generation Sequencing ◽  
Islet Autoantibodies ◽  
Next Generation ◽  
Childhood Type 1 Diabetes ◽  
Childhood Type ◽  
Generation Sequencing

scholarly journals Next-generation sequencing for viruses in children with rapid-onset type 1 diabetes

Diabetologia ◽  
2013 ◽  
Vol 56 (8) ◽  
pp. 1705-1711 ◽  
Author(s):  
H.-S. Lee ◽  
◽  
T. Briese ◽  
C. Winkler ◽  
M. Rewers ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Next Generation Sequencing ◽  
Rapid Onset ◽  
Next Generation ◽  
Onset Type ◽  
Generation Sequencing

scholarly journals Next Generation Sequencing Reveals the Association of DRB3*02:02 With Type 1 Diabetes

Diabetes ◽  
2013 ◽  
Vol 62 (7) ◽  
pp. 2618-2622 ◽  
Author(s):  
H. A. Erlich ◽  
A. M. Valdes ◽  
S. L. McDevitt ◽  
B. B. Simen ◽  
L. A. Blake ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Generation Sequencing

Characterization of the novel HLA‐DQA1 *05:19 allele by next‐generation sequencing

HLA ◽  
2021 ◽  
Author(s):  
Steve Genebrier ◽  
Paul Rouzaire ◽  
Emeric Texeraud ◽  
Gerald Bertrand ◽  
Virginie Renac
Keyword(s):  
Next Generation Sequencing ◽  
The Novel ◽  
Next Generation ◽  
Hla Dqa1 ◽  
Generation Sequencing

Characterization of the novel HLA‐DQA1 *01:80 allele by next generation sequencing

HLA ◽  
2021 ◽  
Author(s):  
Valentine Jacob ◽  
Fabienne Farce ◽  
Rangolie Kaveri ◽  
Judith Desoutter ◽  
Nicolas Guillaume
Keyword(s):  
Next Generation Sequencing ◽  
The Novel ◽  
Next Generation ◽  
Hla Dqa1 ◽  
Generation Sequencing

Prenatal Diagnosis of Tyrosinemia Type 1 Using Next Generation Sequencing

2016 ◽  
Vol 35 (4) ◽  
pp. 282-285 ◽  
Author(s):  
Maryam Rafati ◽  
Faezeh Mohamadhashem ◽  
Azadeh Hoseini ◽  
Somayeh Darzi Ramandi ◽  
Saeed Reza Ghaffari
Keyword(s):  
Prenatal Diagnosis ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Tyrosinemia Type 1 ◽  
Generation Sequencing

P139 False homozygosity observed for one sample’s HLA genotyping on two independent next generation sequencing platforms

2016 ◽  
Vol 77 ◽  
pp. 139
Author(s):  
Zahra Kashi ◽  
Meagan Barner ◽  
Jenefer Dekoning ◽  
Gabriel Caceres ◽  
RaeAnna Neville ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Next Generation ◽  
Hla Genotyping ◽  
Sequencing Platforms ◽  
Generation Sequencing

scholarly journals Deconstruction of HLA-DRB1*04:01:01 and HLA-DRB1*15:01:01 class II haplotypes using next-generation sequencing in European-Americans with multiple sclerosis

2018 ◽  
Vol 25 (6) ◽  
pp. 772-782 ◽  
Author(s):  
Lisa E Creary ◽  
Kalyan C Mallempati ◽  
Sridevi Gangavarapu ◽  
Stacy J Caillier ◽  
Jorge R Oksenberg ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Next Generation Sequencing ◽  
Class Ii ◽  
Effect Sizes ◽  
Molecular Architecture ◽  
Next Generation ◽  
European Americans ◽  
Resolution Level ◽  
Hla Dqa1 ◽  
Generation Sequencing

Background: The association between HLA-DRB1*15:01 with multiple sclerosis (MS) susceptibility is well established, but the contribution of the tightly associated HLA-DRB5*01:01 allele has not yet been completely ascertained. Similarly, the effects of HLA-DRB1*04:01 alleles and haplotypes, defined at the full-gene resolution level with MS risk remains to be elucidated. Objectives: To characterize the molecular architecture of class II HLA-DR15 and HLA-DR4 haplotypes associated with MS. Methods: Next-generation sequencing was used to determine HLA-DQB1, HLA-DQA1, and HLA-DRB1/4/5 alleles in 1403 unrelated European-American patients and 1425 healthy unrelated controls. Effect sizes of HLA alleles and haplotypes on MS risk were measured by odds ratio (OR) with 95% confidence intervals. Results: HLA-DRB1*15:01:01:01SG (OR = 3.20, p < 2.2E–16), HLA-DRB5*01:01:01 (OR = 2.96, p < 2.2E–16), and HLA-DRB5*01:01:01v1_STR1 (OR = 8.18, p = 4.3E–05) alleles all occurred at significantly higher frequencies in MS patients compared to controls. The most significant predis-posing haplotypes were HLA-DQB1*06:02:01~ HLA-DQA1*01:02:01:01SG~HLA-DRB1*15:01:01:01SG~HLA-DRB5*01:01:01 and HLA-DQB1*06:02:01~HLA-DQA1*01:02:01:01SG~HLA-DRB1*15:01:01:01SG~HLA-DRB5*01:01:01v1_STR1 (OR = 3.19, p < 2.2E–16; OR = 9.30, p = 9.7E–05, respectively). Analyses of the HLA-DRB1*04 cohort in the absence of HLA-DRB1*15:01 haplotypes revealed that the HLA-DQB1*03:01:01:01~HLA-DQA1*03:03:01:01~HLA-DRB1*04:01:01:01SG~HLA-DRB4*01:03:01:01 haplotype was protective (OR = 0.64, p = 0.028), whereas the HLA-DQB1*03:02:01~HLA-DQA1*03:01:01~HLA-DRB1*04:01:01:01SG~HLA-DRB4*01:03:01:01 haplotype was associated with MS susceptibility (OR = 1.66, p = 4.9E–03). Conclusion: HLA-DR15 haplotypes, including genomic variants of HLA-DRB5, and HLA-DR4 haplotypes affect MS risk.

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