Genes for covid-19 resilience: identification of DNA markers corresponding to coronavirus resistance and susceptibility

Dr. Timothy Sexton

Coronaviruses 004 lores


Coronaviruses (CoVs) (order Nidovirales, family Coronaviridae, subfamily Coronavirinae) are responsible for respiratory disease outbreaks in many vertebrate species. They are a large family of single-stranded RNA enveloped viruses (+ssRNA) that can be isolated in different animal species. They have genome sizes ranging between 26 to 32 kilobases (kb) in length, being the largest genomes for RNA viruses (consequently increasing the effectiveness of facemasks). COVID-19 also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 2019-nCoV or "novel coronavirus 2019" is a new virus with no known resistance in humans.


COVID-19 is similar to severe acute respiratory syndrome (SARS) in the respect that both viruses infect their human hosts via the same receptor, the angiotensin-converting enzyme 2 (ACE2 receptor), and cause similar clinical and pathological features. Interestingly the spike protein which is responsible for receptor binding is highly similar between 2019-nCoV and SARS-CoV, this is a result of significant selection for the same receptor (Wu., 2020).


Research into how our bodies defend against other viruses has revealed several strategies our bodies may use to protect us from covid-19. Based on current infections we know that some individuals are virtually unaffected, they can be asymptomatic, while sadly the covid-19 virus has proven to be fatal for thousands of people especially those who are vulnerable.


If you have taken an at home DNA test like those available from 23andMe, Ancestry DNA, Dante labs and other providers including DNA Romance. In this post information is presented a candidate gene for SARS-CoV resistance.


How to analyze your DNA for coronavirus resistance and susceptibility markers?


Step 1) Download your raw autosomal DNA file and save it to a safe and secure location

To analyze your DNA data, start by downloading your raw autosomal DNA and save it to a safe location. Here are instructions to download your raw DNA file from: 23andMe, Ancestry DNA, Family Tree DNA, Dante Labs, My Heritage, Genes For Good, Vitagene, and Living DNA.


Step 2) Analyze your raw DNA file


It simple to manually search your raw DNA data using a text editor such as "text wrangler" or "notepad" using the "find" function

Open the raw DNA file and your will notice the headers of unique SNP ID (rs# or i#), chromosome, position and genotype. The formats differ slightly between each DNA testing company


To evaluate your risk of poor recovery from the coronavirus SARS, HIV, tuberculosis have a look for this SNP:

The SNP rs4804803 can prevent the gene expression of the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin protein, DC-SIGN for short and in humans the CD209 gene encodes this protein where the G allele is associated with transcription factor binding, and the A allele with its absence (Sakuntabhai et al., 2005). For rs4804803 the G alleles (A:G) or (G:G) have 2.5x greater greater chance of having lower lactate dehydrogenase (LDH) levels compared with -336AA patients. High LDH levels are known to be an independent predictor for poor SARS clinical outcome, possibly because of the increased tissue destruction that is the result of immune hyperactivity. Thus, SARS patients with the AA genotype have a 60% greater chance of a poor prognosis than GG or AG patients, for more details see Chan et al., 2010.



Other DNA markers covered in this post include SNPs positioned in the angiotensin-converting enzyme-2 (ACE2) receptor which was proved to be the receptor for the human respiratory coronavirus NL63 (Li et al., 2017, SARS-coronavirus (SARS-CoV), and the novel coronavirus 2019-nCoV/SARS-CoV (Lu et al., 2019). Since the spike protein of the coronavirus has evolved to match the ACE2 receptor (Wu., 2020), it's likely that individuals with variations that alter the protein sequence would result in a degree of resistance to covid-19. Below non-synonymous SNPs from the ACE2 transcript NM_021804.2 are presented from Cao et al., 2020. Of particular interest are the 3 SNPs highlighted in red which cause major changes to the ACE 2 receptor, rs199951323 results in a premature stop codon, it’s hoped that alleles in the "ALT" category would result in some degree of covid-19 resistance since the virus would find it more difficult to bind to the hosts cells.


dbsnp Chromosome POS REF ALT Function Transcript NM_021804.2 (3'-5' on genome)
NA chrX 15561921 A C missense_variant p.Val801Gly/c.2402T>G
rs373153165 chrX 15561970 C T missense_variant p.Asp785Asn/c.2353G>A
NA chrX 15562011 T C missense_variant+splice_region_variant p.Lys771Arg/c.2312A>G
NA chrX 15562020 A C splice_region_variant+intron_variant c.2310-7T>G
rs140016715 chrX 15564031 G A missense_variant p.Arg768Trp/c.2302C>T
NA chrX 15564075 A G missense_variant p.Ile753Thr/c.2258T>C
NA chrX 15564142 G T missense_variant p.Leu731Ile/c.2191C>A
rs147311723 chrX 15564142 G A missense_variant p.Leu731Phe/c.2191C>T
NA chrX 15564154 T C missense_variant p.Ile727Val/c.2179A>G
rs41303171 chrX 15564175 T C missense_variant p.Asn720Asp/c.2158A>G
rs370187012 chrX 15564204 C T missense_variant p.Arg710His/c.2129G>A
rs776995986 chrX 15564211 G A missense_variant p.Arg708Trp/c.2122C>T
rs149039346 chrX 15566293 A G missense_variant p.Ser692Pro/c.2074T>C
rs200180615 chrX 15566365 C T missense_variant p.Glu668Lys/c.2002G>A
NA chrX 15567751 C T missense_variant p.Val658Ile/c.1972G>A
rs199951323 chrX 15567756 A C stop_gained p.Leu656*/c.1967T>G
rs183135788 chrX 15567810 T C missense_variant p.Asn638Ser/c.1913A>G
rs748163894 chrX 15570311 G A missense_variant Change to transcript NM_021804.2
NA chrX 15571687 A G missense_variant p.Phe592Leu/c.1774T>C
NA chrX 15571737 C A missense_variant p.Gly575Val/c.1724G>T
rs202137736 chrX 15573362 T C splice_region_variant+intron_variant c.1541+5A>G
rs140473595 chrX 15573407 C T missense_variant p.Ala501Thr/c.1501G>A
rs191860450 chrX 15575706 T C missense_variant p.Ile468Val/c.1402A>G
NA chrX 15578237 C T missense_variant p.Met383Ile/c.1149G>A
NA chrX 15585477 G A stop_gained+splice_region_variant p.Gln300*/c.898C>T
NA chrX 15587858 T A missense_variant+splice_region_variant p.Ile233Phe/c.697A>T
rs758142853 chrX 15591745 A G missense_variant p.Val184Ala/c.551T>C
rs754511501 chrX 15591779 C T missense_variant p.Gly173Ser/c.517G>A
rs746034076 chrX 15591820 T C missense_variant p.Asn159Ser/c.476A>G
rs373252182 chrX 15591850 T C missense_variant p.Asn149Ser/c.446A>G
rs2285666 chrX 15592225 C T splice_region_variant+intron_variant c.439+4G>A
rs768736934 chrX 15594840 C T splice_region_variant+intron_variant c.345+5G>A
NA chrX 15594841 G T splice_region_variant+intron_variant c.345+4C>A
NA chrX 15600798 G C missense_variant p.Asp38Glu/c.114C>G
NA chrX 15600815 T C missense_variant p.Asn33Asp/c.97A>G
rs4646116 chrX 15600835 T C missense_variant p.Lys26Arg/c.77A>G
NA chrX 15600850 A G missense_variant p.Ile21Thr/c.62T>C
rs73635825 chrX 15600857 A G missense_variant p.Ser19Pro/c.55T>C
NA chrX 15601012 G T splice_region_variant c.-101C>A
NA chrX 15601015 C A splice_acceptor_variant+intron_variant c.-103-1G>T

One interesting observation to note is that the ACE2 gene is positioned on the X chromosome, meaning that men will only inherit one copy of this gene. The additional diversity provided by the females 2nd copy of the ACE2 gene on their 2nd X chromosome could in part help to explain why women are less susceptible to covid-19.


Step 3) Compare your genotype with research findings

There are a wealth of resources describing information for relating to this SNP check out dbSNP and SNPedia


dbSNP

dbSNP contains human single nucleotide variations, microsatellites, and small-scale insertions and deletions along with publication, population frequency, molecular consequence, and genomic and RefSeq mapping information for both common variations and clinical mutations.


SNPpedia

SNPedia is a wiki investigating human genetics. They share information about the effects of variations in DNA, citing peer-reviewed scientific publications. It is used by Promethease to create a personal report linking your DNA variations to the information published about them.



**If you are concerned about anything you see in your DNA results, please speak to your doctor, or a genetics councillor




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