Among its related pathways are Viral mRNA Translation and Measles. Gene Ontology (GO) annotations related to this gene include transmembrane signaling receptor activity and double-stranded RNA binding (dsRBD). An important paralog of this gene is TLR8.
A variant in itself is not “pathogenic”, whether it can be causally related to a phenotype observed in a patient is determined by other factors. When a variant is described to "cause disease", the expert probably means “causes disease in a specific context”, e.g:
Immunodeficiency-74 (IMD74) is also an X-linked recessive specific immunologic disorder characterized by the development of severe respiratory insufficiency in response to infection with the COVID19 coronavirus.[6]
The 23andMe genotyping platform detects single nucleotide polymorphisms (SNPs).[10] A SNP is a DNA location, or "marker," in the genome that has been shown to vary among people in terms of the DNA base or bases. There are four DNA bases:
In this article, we will cover the below topics:
- Genetic Variation
- X-linked COVID-19 Risk Factor
- Raw Data on Your Genetic Data (23andMe)
- How Does 23andMe Report Genotypes?
- All Markers Reported on 23andMe for TLR7 Gene
Genetic Variation
Genetic variation is the difference in DNA sequences between individuals within a population. Variants may be germline or somatic.
A variant in itself is not “pathogenic”, whether it can be causally related to a phenotype observed in a patient is determined by other factors. When a variant is described to "cause disease", the expert probably means “causes disease in a specific context”, e.g:
- X-linked recessive disorder
- Causes disease when found in a male
- Autosomal recessive
- Causes disease when combined with a change on the other allele
- Imprinting disorder
- Causes disease when inherited from the father
X-linked COVID-19 Risk Factor
Age and male sex are two prominent risk factors for developing life-threatening COVID-19 after SARS-CoV-2 infection.
Asano et al. analyzed 1202 critical male COVID-19 patients to examine whether non-synonymous variants in genes on the X chromosome are a risk factor for developing COVID-19 pneumonia. TLR7 variants resulting in TLR7 deficiency occurred in 16 unrelated males, most of which were under age 60.[2]
Plasmacytoid dendritic cells (pDCs), primary producers of type I interferon (IFN-I), from TLR7-deficient patients were unresponsive to TLR7 stimulation and displayed impaired production of IFN-I in response to SARS-CoV-2. These results identify X-linked recessive TLR7 deficiency as a genetic risk factor for COVID-19 pneumonia in males and demonstrate a key role for intact pDC IFN-I in protective immunity against SARS-CoV-2.
Immunodeficiency-74 (IMD74)
Affected individuals usually require mechanical ventilation in the ICU in order to survive. Laboratory studies show activation of the immune response and may show perturbation of some values, such as increased D-dimers and fibrinogen.
In vitro functional studies of patient immune cells show impaired signaling through the TLR7 pathway, resulting in defective type I and type II interferon (IFN) responses. The patients reported to date did not have a history of immunodeficiency or chronic disease.[6]
Raw Data on Your Genetic Data (23andMe)
23andMe uses genotyping, not sequencing, to analyze your DNA. Read [10] for more details.
How Does 23andMe Report Genotypes?
So, for example, at the same genomic location, you might have a C and someone else might have a T. These DNA base differences are known as "variants."
For most SNPs on the 23andMe platform, the 23andMe Raw Data feature reports the marker name (usually an rsID or internal ID number), its exact genomic location, the possible variants at that marker (A, T, G, or C), and the specific variants you have, i.e. your genotype (See Table 1).
For most SNPs on the 23andMe platform, the 23andMe Raw Data feature reports the marker name (usually an rsID or internal ID number), its exact genomic location, the possible variants at that marker (A, T, G, or C), and the specific variants you have, i.e. your genotype (See Table 1).
Because you have two sets of autosomal chromosomes -- one from your mother and one from your father -- you usually have two variants at every location, and your genotype will be reported as a pair of variants, e.g. "G/A."
In some cases your genotype will be reported as a single variant because not all DNA is inherited in chromosome pairs e.g., mitochondrial DNA and, for the most part, the X and Y chromosomes in men).
Occasionally, for some SNPs on the 23andMe platform, your genotype may be reported as an insertion or deletion (--) of DNA bases instead of just a simple variant pair.
In some cases your genotype will be reported as a single variant because not all DNA is inherited in chromosome pairs e.g., mitochondrial DNA and, for the most part, the X and Y chromosomes in men).
Occasionally, for some SNPs on the 23andMe platform, your genotype may be reported as an insertion or deletion (--) of DNA bases instead of just a simple variant pair.
Depending on the genomic location, either an insertion or deletion could represent the typical version of the SNP. In other words, there are some markers in which having an extra base (insertion) is the typical variant and having a deletion is the less common variant. Conversely, there are some places in the genome where an insertion is rare, making a deletion the typical variant at that location.23andMe does not report on all possible insertions or deletions. In general, the ones reported on are small, spanning only one or a few bases.
All Markers Reported on 23andMe for TLR7 Gene
On 23andMe, you can search for specific genes, markers, or positions of interest. For example, here are the list of markers found by searching with TLR7 keyword:
- rs2302267
- rs5741880
- rs1731479 (intron variant)
- See Table 2
- rs5743740
- rs5743749
- rs179012
- rs179010
- rs179008
- rs864058
 |
| Table 2. TLR7 with NM_016562.4:c.3+4753C>T change |
However, 23andMe uses genotyping, not sequencing, to analyze your DNA. So, not all markers or positions are tested by 23andMe. They only look for variants of interest at the time of testing.[10,11]
Genotyping can be performed through a variety of different methods, depending on the variants of interest and the resources available. For looking at many different variants at once, especially common variants, genotyping chips are an efficient and accurate method. They do, however, require prior identification of the variants of interest.
References
- When the Immune Response Makes COVID-19 Worse
- X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19
- TLR7 Gene
- Immunodeficiency 74, Covid19-Related, X-Linked
- Genotyping: Terms to know
- Presence of Genetic Variants Among Young Men With Severe COVID-19
- Designing spatial and temporal control of vaccine responses
- HGVS simple (important)
- RefSNP Report Help (important)
- How does 23andMe report genotypes?
- Difference Between DNA Genotyping & Sequencing
- Raw Genotype Data Technical Details (23andme)
- Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus
- Note that none of the markers (or variants) mentioned in this article were tested by 23andme.
- Had COVID but no symptoms? You might have this genetic mutation
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