Whole genome sequencing identifies novel candidate genetic variants in canine stomatocytosis

被引：0
作者：
Wallace, M. D. [1 ,2 ,4 ]
Falcone, S. [2 ,4 ]
Castillo, D. [3 ]
Williams, T. L. [3 ]
Davison, L. J. [1 ,2 ,4 ]
机构：
[1] Royal Vet Coll, Clin Sci & Serv, Hawkshead Lane, Hatfield AL9 7TA, England
[2] Univ Oxford, Wellcome Ctr Human Genet, Oxford OX3 7BN, England
[3] Univ Cambridge, Dept Vet Med, Madingley Rd, Cambridge CB3 0ES, England
[4] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England
来源：
GENE | 2025年 / 945卷
基金：
英国惠康基金;
关键词：
Stomatocytosis; Hematology; Erythrocytes; Genomics; Whole genome sequencing; Red blood cell; RED-BLOOD-CELLS; HEREDITARY STOMATOCYTOSIS; STANDARD SCHNAUZERS; TRANSPORT; MUTATION; BROWSER; DISEASE; DOGS; SET;
D O I：
10.1016/j.gene.2025.149314
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Stomatocytosis is a rare spectrum of red blood cell (RBC) disorders. In humans, stomatocytosis is typically caused by genetic changes in specific ion exchange and transport genes. Stomatocytosis has been identified in dogs, however the underlying genetic causes are unknown. Recently, stomatocytosis was reported in a Beagle and Australian Cattle Dog for the first time. Here, whole-genome sequencing (WGS) of these dogs was undertaken to identify candidate genetic variants driving or impacting stomatocytosis. Cases were compared to WGS of 119 controls of several breeds and > 1,000 dogs from public and private datasets. Candidate genes were identified, including genes linked to stomatocytosis in humans: SPTB and KCNN4. Notably, each case carried a different homozygous intronic SNP in SPTB only 24 bases apart (Beagle - chr8:39,194,923; ACD - chr8:39,194,947; CanFam3.1), which were not homozygous in other dogs. Variants with predicted deleterious impact in additional ion transport-related genes were also identified: SLC8A3, DYSF, SLC12A8, INPP5E, SLC1A1, and a novel SLC41A3 genetic change carried by the Australian Cattle Dog. Human and mouse scRNAseq and proteomics data indicate that these candidate genes are expressed in RBCs or their immature precursors. Taken together, these genetic data obtained from spontaneous stomatocytosis in a non-human species provide novel insights and candidate genes for evaluation of rare red cell disorders in humans.
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页数：14
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