Browsing by Author "Zhao, Pei"

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    ConVarT: A search engine for matching human genetic variants with variants from non-human species
    (Oxford University Press, 2022) Pir, Mustafa; Bilgin, Halil I.; Sayıcı, Ahmet; Coşkun, Fatih; Torun, Furkan M; Zhao, Pei; Kang, Yahong; Çevik, Sebiha; Kaplan, Oktay İsmail; 0000-0002-8733-0920; 0000-0002-0935-1929; AGÜ, Mühendislik Fakültesi, Bilgisayar Mühendisliği Bölümü; Pİr, Mustafa; Bilgin, Halil İbrahim; Sayıcı, Ahmet; Coşkun, Fatih; Torun, Furkan M.; Çevik, Sebiha; Kaplan, Oktay İsmail
    The availability of genetic variants, together with phenotypic annotations from model organisms, facilitates comparing these variants with equivalent variants in humans. However, existing databases and search tools do not make it easy to scan for equivalent variants, namely 'matching variants' (MatchVars) between humans and other organisms. Therefore, we developed an integrated search engine called ConVarT (http://www.convart.org/) for matching variants between humans, mice, and Caenorhabditis elegans. ConVarT incorporates annotations (including phenotypic and pathogenic) into variants, and these previously unexploited phenotypic MatchVars from mice and C. elegans can give clues about the functional consequence of human genetic variants. Our analysis shows that many phenotypic variants in different genes from mice and C. elegans, so far, have no counterparts in humans, and thus, can be useful resources when evaluating a relationship between a new human mutation and a disease.
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    Matching variants for functional characterization of genetic variants
    (Genetics Society of America, 2023) Cevik-Kaplan, Sebiha; Zhao, Pei; Zorluer, Atiyye; Pir, Mustafa Samet; Bian, Wenyin; 0000-0002-0935-1929; 0000-0002-8733-0920; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Cevik-Kaplan, Sebiha; Zorluer, Atiyye; Pir, Mustafa Samet; Kaplan, Oktay Ismaıl
    Rapid and low-cost sequencing, as well as computer analysis, have facilitated the diagnosis of many genetic diseases, resulting in a substantial rise in the number of disease-associated genes. However, genetic diagnosis of many disorders remains problematic due to the lack of interpretation for many genetic variants, especially missenses, the infeasibility of high-throughput experiments on mammals, and the shortcomings of computational prediction technologies. Additionally, the available mutant databases are not well-utilized. Toward this end, we used Caenorhabditis elegans mutant resources to delineate the functions of eight missense variants (V444I, V517D, E610K, L732F, E817K, H873P, R1105K, and G1205E) and two stop codons (W937stop and Q1434stop), including several matching variants (MatchVar) with human in ciliopathy associated IFT-140 (also called CHE-11)//IFT140 (intraflagellar transport protein 140). Moreover, MatchVars carrying C. elegans mutants, including IFT-140(G680S) and IFT-140(P702A) for the human (G704S) (dbSNP: rs150745099) and P726A (dbSNP: rs1057518064 and a conflicting variation) were created using CRISPR/Cas9. IFT140 is a key component of IFT complex A (IFT-A), which is involved in the retrograde transport of IFT along cilia and the entrance of G protein-coupled receptors into cilia. Functional analysis of all 10 variants revealed that P702A and W937stop, but not others phenocopied the ciliary phenotypes (short cilia, IFT accumulations, mislocalization of membrane proteins, and cilia entry of nonciliary proteins) of the IFT-140 null mutant, indicating that both P702A and W937stop are phenotypic in C. elegans. Our functional data offered experimental support for interpreting human variants, by using ready-to-use mutants carrying MatchVars and generating MatchVars with CRISPR/Cas9.