Rarity and Disparity in Genomics

Asuragen is a biotechnology company based in Austin, Texas that is driving the evolution of precision medicine in inherited disorders. They have developed assays to characterize dark DNA, raising its potential for clinical research and helping to translate these advances into diagnostic technology.

The Asuragen AmplideX suite of products uses novel long-read PCR coupled with capillary electrophoresis–based fragment analysis to solve unmet testing needs in inherited genetic disorders by amplifying the dark DNA regions of interest. To provide routine and accessible analysis of DNA using capillary electrophoresis, Asuragen uses the Applied Biosystems SeqStudio Genetic Analyzer. Compared to traditional Southern blotting or other methods, the SeqStudio instrument delivers high-quality data within hours rather than days, with a simple, straightforward workflow.

Read the blog post to find out how Asuragen is using the SeqStudio to help advance the understanding of inherited disorders
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Ataxia-telangiectasia (A-T), or Louis-Bar syndrome, is a rare inherited disorder that tends to manifest in early childhood and has no known cure. Symptoms include progressive difficulty in coordinating movements and increased susceptibility to cancer and infections. The disease is caused by mutations in the ATM gene, which produces a protein that helps control cell division and DNA repair.

The ATM gene, which is 150 kb long, gives rise to more than 600 pathogenic variants, with more being discovered each year. Variations in this gene can be explored using next-generation sequencing technology, making it possible to detect both known and novel mutations.

Scientists at the Research Center for Obstetrics, Gynecology, and Perinatology in Moscow, Russia were able to detect two novel mutations in the ATM gene, each in a family with one or more children affected with A-T². Both families had sought genetic counseling because the mothers were in the early months of pregnancy and were hoping for prenatal diagnosis.

Using the Ion AmpliSeq Inherited Disease Panel on an Ion PGM instrument, researchers performed complete ATM gene sequencing on a single member of each family. As a result, a formerly unknown SNP was attributed to each family. In the first family, there wasa single-nucleotide deletion in exon 48; in the second, a single-nucleotide insertion in exon 9 was found. Both of these mutations resulted in truncation of the ATM protein.

After identifying the location of these mutations, prenatal diagnosis was later performed through standard medical procedures. Fortunately, both fetuses had a healthy genotype and were not expected to develop A-T.

The discovery of these mutations has allowed these two families to plan for a promising future with their children, equipped with this new information. Additionally, the mutations have been submitted to appropriate databases such as ClinVar and the Leiden Open Variation Database (LOVD).

Learn more about Ion Torrent NGS solutions for inherited disease research

With a population of over one billion people and life expectancies of around 56 years, sub-Saharan Africa offers the opportunity to address health care disparities at population and worldwide scales. Take prostate cancer, for example: men of African descent, globally, experience a higher incidence with poorer outcomes than other population groups. To address this, investigators from Africa, the Caribbean, the US, and the UK formed the Men of African Descent and Carcinoma of the Prostate (MADCaP) Consortium.

One key objective was the first-ever large- scale genome-wide association study (GWAS) on the African continent. However, GWAS has been biased toward European populations, historically, and so new SNP genotyping tools were required.

With the bioinformatics expertise of the team from Thermo Fisher Scientific, MADCaP investigators designed a genotyping microarray optimized for African genomic variation. With over 1.5 million SNPs and other variants, it offers new opportunities to discover genetic risk factors in these understudied populations. MADCaP is now exploring how to make the microarray available to other research groups to extend the potential impact on health care disparities.

Visit the blog to learn more about the MADCaP Consortium’s research strategy and the Applied Biosystems Axiom genotyping microarray they developed
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