Analysis of Gene Targeting Techniques for Huntington’s Disease and Gene Expression in Human Cells

Gemstone Team CHANGEHuntington’s disease (HD) is an inherited neurodegenerative disorder that is caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. Our team performed a literature analysis to investigate the current state of research for treating HD and identified a new technology called prime editing that could be applied to HD in combination with single nucleotide polymorphisms (SNPs). We found that at least 729 SNPs within the HTT gene are compatible with our proposed approach. Experimentally, we performed preliminary studies using Western Blots and RT-qPCR to examine the differences in expression of HTT in a variety of cell lines. Our literature-based work suggests that prime editing is a promising tool for addressing the basis of a variety of genetic disorders. Our experimental-based work confirms that human fibroblast cells express HTT and therefore may be used in proof of concept studies of gene targeting techniques to address HD

Gene Targeting Techniques for Huntington's Disease

Huntington’s disease (HD) is an autosomal neurodegenerative disorder caused by extended trinucleotide CAG repetition in the HTT gene. Although this mutation in the HTT gene is mostly associated with neurological and physical symptoms that HD typically exhibits, wild-type Huntingtin protein (HTT) is involved in a variety of cellular functions such as vesicle transportation, cell division, transcription regulation, autophagy, and tissue maintenance. The main cause of HD symptoms is due to aggregation and accumulation of mutant HTT (mHTT) proteins in neurons. In this review, we discuss multiple approaches targeting DNA and RNA to reduce mHTT expression. These approaches are categorized into non-allele-specific silencing and allele-specific-silencing using SNPs and haplogroup analysis, and the possible limitations of targeting mHTT is also discussed. Additionally, this review discusses am potential appliction of recent CRISPR prime editing technology in treating HD

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19

The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.</p