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- Johannsen, Emma B., et al.
(författare)
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The genetics of sudden infant death syndrome—towards a gene reference resource
- 2021
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Sudden infant death syndrome (SIDS) is the unexpected death of an infant under one year of age that remains unexplained after a thorough investigation. Despite SIDS remaining a diagnosis of exclusion with an unexplained etiology, it is widely accepted that SIDS can be caused by environmental and/or biological factors, with multiple underlying candidate genes. However, the lack of biomarkers raises questions as to why genetic studies on SIDS to date are unable to provide a clearer understanding of the disease etiology. We sought to improve the identification of SIDS-associated genes by reviewing the SIDS genetic literature and objectively categorizing and scoring the reported genes based on the strength of evidence (from C1 (high) to C5 (low)). This was followed by analyses of function, associations between genes, the enrichment of gene ontology (GO) terms, and pathways and gender difference in tissue gene expression. We constructed a curated database for SIDS gene candidates consisting of 109 genes, 14 of which received a category 4 (C4) and 95 genes received the lowest category of C5. That none of the genes was classified into the higher categories indicates the low level of supporting evidence. We found that genes of both scoring categories show distinct networks and are highly diverse in function and involved in many GO terms and pathways, in agreement with the perception of SIDS as a heterogeneous syndrome. Genes of both scoring categories are part of the cardiac system, muscle, and ion channels, whereas immune-related functions showed enrichment for C4 genes. A limited association was found with neural development. Overall, inconsistent reports and missing metadata contribute to the ambiguity of genetic studies. Considering those parameters could help improve the identification of at-risk SIDS genes. However, the field is still far from offering a full-pledged genetic test to identify at-risk infants and is still hampered with methodological challenges and misunderstandings of the vulnerabilities of vital biological mechanisms.
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| 2. |
- Baughn, Linda B., et al.
(författare)
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Targeting TMPRSS2 in SARS-CoV-2 Infection
- 2020
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Ingår i: Mayo Clinic Proceedings. - : Elsevier BV. - 0025-6196. ; 95:9, s. 1989-1999
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has rapidly caused a global pandemic associated with a novel respiratory infection: coronavirus disease-19 (COVID-19). Angiotensin-converting enzyme-2 (ACE2) is necessary to facilitate SARS-CoV-2 infection, but—owing to its essential metabolic roles—it may be difficult to target it in therapies. Transmembrane protease serine 2 (TMPRSS2), which interacts with ACE2, may be a better candidate for targeted therapies. Using publicly available expression data, we show that both ACE2 and TMPRSS2 are expressed in many host tissues, including lung. The highest expression of ACE2 is found in the testes, whereas the prostate displays the highest expression of TMPRSS2. Given the increased severity of disease among older men with SARS-CoV-2 infection, we address the potential roles of ACE2 and TMPRSS2 in their contribution to the sex differences in severity of disease. We show that expression levels of ACE2 and TMPRSS2 are overall comparable between men and women in multiple tissues, suggesting that differences in the expression levels of TMPRSS2 and ACE2 in the lung and other non–sex-specific tissues may not explain the gender disparities in severity of SARS CoV-2. However, given their instrumental roles for SARS-CoV-2 infection and their pleiotropic expression, targeting the activity and expression levels of TMPRSS2 is a rational approach to treat COVID-19.
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