Robin McDonald
Robin McDonald
Robin McDonald
Helios Scholar
School: Arizona School for the Arts
Hometown: Sonoma, California
Mentor: Winnie Liang, Ph.D.

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Human leukocyte antigen (HLA) typing for ALS

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons and that leads to the loss of voluntary muscle control. The exact cause of ALS, or an effective treatment to halt or reverse the disease, has yet to be determined. Several genes identified in association with familial ALS suggest that a number of factors including oxidative stress, glutamate excitotoxicity, and protein misfolding may drive development of the disease. In other neurological diseases including multiple sclerosis, human leukocyte antigen (HLA) genes have been reported to be associated with disease susceptibility. The highly polymorphic HLA genes code for peptide-presenting major histocompatibility complexes and are also associated with over 100 autoimmune diseases. Given the neurodegenerative nature of ALS, it is hypothesized that HLA alleles may be correlated with ALS.

For this study, we looked for an association between 11 HLA loci (A, B, C, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1, DQA1, DQB2) and ALS. We sequenced DNA obtained from peripheral blood from ALS patients (n=21) and controls (n=14) using the Illumina TruSight HLA v2 Sequencing Panel on the Illumina MiSeq. HLA genes are known to reflect population demography; therefore, to test for associations between the ALS cohort and control population, patients must be paired to controls with similar demography. Unfortunately, the demographic information for the controls was not provided for this study. We were unable to predict demographic information of the controls following population clustering and review of the Allele Frequency Net HLA Database. Therefore, we analyzed Caucasian ALS cases (n=16) matched to HLA database controls (n=268). Analysis was performed on all 11 HLA loci to determine allele frequencies, odds ratios, confidence intervals, and p-values (using a two-tailed Fisher’s exact test) for each allele. Significant results (p<0.01) were identified at alleles HLA-A*11:01 and HLA-DQA1*05:01. Previous studies using serotype data found associations at HLA-A3 and HLA-B35. These results provide evidence of an association between HLA loci and ALS to suggest that they may act as potential biomarkers of disease.