Abstract:During the maintenance of the wild silkworm, Bombyx mandarina, a mutant phenotype exhibiting translucent skin was identified. Based on the crossing experiments with the domesticated silkworm, Bombyx mori, we found that the mutant was controlled by molybdenum cofactor sulfurase (MoCoS) gene. We designated the mutant ''Ozaki's translucent'' (og Z ). We found a 2.1-kb deletion containing the transcription initiation site, exons 1 and 2, and the 5' end of exon 3 of the MoCoS gene. The transcript of the MoCoS gene … Show more
“…MOCOS is therefore part of a complex pathway and the object of studies at different levels and expression studies associating the protein with genes involved in regulating transcription and apoptosis [31]. In wild silkworms, a MOCOS loss of function mutation was reported showing a mutant phenotype resulting in translucent skin [32]. In humans, mutations in MOCOS cause type II xanthinuria (OMIM 613274; Fig.…”
Section: Resultsmentioning
confidence: 99%
“…A MOCOS c.466G > C missense mutation (p.Ala156Pro) was described in another xanthinuric patient [34]. Finally, a homozygous MOCOS c.2326C > T missense mutation (p.Arg776Cys), and a compound heterozygous with a MOCOS c.1034insA nonsense mutation (p.Gln347fs32*) was present in a further two xanthinuria patients [32]. Fig.…”
BackgroundRenal syndromes are occasionally reported in domestic animals. Two identical twin Tyrolean Grey calves exhibited weight loss, skeletal abnormalities and delayed development associated with kidney abnormalities and formation of uroliths. These signs resembled inherited renal tubular dysplasia found in Japanese Black cattle which is associated with mutations in the claudin 16 gene. Despite demonstrating striking phenotypic similarities, no obvious presence of pathogenic variants of this candidate gene were found. Therefore further analysis was required to decipher the genetic etiology of the condition.ResultsThe family history of the cases suggested the possibility of an autosomal recessive inheritance. Homozygosity mapping combined with sequencing of the whole genome of one case detected two associated non-synonymous private coding variants: A homozygous missense variant in the uncharacterized KIAA2026 gene (g.39038055C > G; c.926C > G), located in a 15 Mb sized region of homozygosity on BTA 8; and a homozygous 1 bp deletion in the molybdenum cofactor sulfurase (MOCOS) gene (g.21222030delC; c.1881delG and c.1782delG), located in an 11 Mb region of homozygosity on BTA 24. Pathogenic variants in MOCOS have previously been associated with inherited metabolic syndromes and xanthinuria in different species including Japanese Black cattle. Genotyping of two additional clinically suspicious cases confirmed the association with the MOCOS variant, as both animals had a homozygous mutant genotype and did not show the variant KIAA2026 allele. The identified genomic deletion is predicted to be highly disruptive, creating a frameshift and premature termination of translation, resulting in severely truncated MOCOS proteins that lack two functionally essential domains. The variant MOCOS allele was absent from cattle of other breeds and approximately 4% carriers were detected among more than 1200 genotyped Tyrolean Grey cattle. Biochemical urolith analysis of one case revealed the presence of approximately 95% xanthine.ConclusionsThe identified MOCOS loss of function variant is highly likely to cause the renal syndrome in the affected animals. The results suggest that the phenotypic features of the renal syndrome were related to an early onset form of xanthinuria, which is highly likely to lead to the progressive defects. The identification of the candidate causative mutation thus enables selection against this pathogenic variant in Tyrolean Grey cattle.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0904-4) contains supplementary material, which is available to authorized users.
“…MOCOS is therefore part of a complex pathway and the object of studies at different levels and expression studies associating the protein with genes involved in regulating transcription and apoptosis [31]. In wild silkworms, a MOCOS loss of function mutation was reported showing a mutant phenotype resulting in translucent skin [32]. In humans, mutations in MOCOS cause type II xanthinuria (OMIM 613274; Fig.…”
Section: Resultsmentioning
confidence: 99%
“…A MOCOS c.466G > C missense mutation (p.Ala156Pro) was described in another xanthinuric patient [34]. Finally, a homozygous MOCOS c.2326C > T missense mutation (p.Arg776Cys), and a compound heterozygous with a MOCOS c.1034insA nonsense mutation (p.Gln347fs32*) was present in a further two xanthinuria patients [32]. Fig.…”
BackgroundRenal syndromes are occasionally reported in domestic animals. Two identical twin Tyrolean Grey calves exhibited weight loss, skeletal abnormalities and delayed development associated with kidney abnormalities and formation of uroliths. These signs resembled inherited renal tubular dysplasia found in Japanese Black cattle which is associated with mutations in the claudin 16 gene. Despite demonstrating striking phenotypic similarities, no obvious presence of pathogenic variants of this candidate gene were found. Therefore further analysis was required to decipher the genetic etiology of the condition.ResultsThe family history of the cases suggested the possibility of an autosomal recessive inheritance. Homozygosity mapping combined with sequencing of the whole genome of one case detected two associated non-synonymous private coding variants: A homozygous missense variant in the uncharacterized KIAA2026 gene (g.39038055C > G; c.926C > G), located in a 15 Mb sized region of homozygosity on BTA 8; and a homozygous 1 bp deletion in the molybdenum cofactor sulfurase (MOCOS) gene (g.21222030delC; c.1881delG and c.1782delG), located in an 11 Mb region of homozygosity on BTA 24. Pathogenic variants in MOCOS have previously been associated with inherited metabolic syndromes and xanthinuria in different species including Japanese Black cattle. Genotyping of two additional clinically suspicious cases confirmed the association with the MOCOS variant, as both animals had a homozygous mutant genotype and did not show the variant KIAA2026 allele. The identified genomic deletion is predicted to be highly disruptive, creating a frameshift and premature termination of translation, resulting in severely truncated MOCOS proteins that lack two functionally essential domains. The variant MOCOS allele was absent from cattle of other breeds and approximately 4% carriers were detected among more than 1200 genotyped Tyrolean Grey cattle. Biochemical urolith analysis of one case revealed the presence of approximately 95% xanthine.ConclusionsThe identified MOCOS loss of function variant is highly likely to cause the renal syndrome in the affected animals. The results suggest that the phenotypic features of the renal syndrome were related to an early onset form of xanthinuria, which is highly likely to lead to the progressive defects. The identification of the candidate causative mutation thus enables selection against this pathogenic variant in Tyrolean Grey cattle.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0904-4) contains supplementary material, which is available to authorized users.
“…Combined with current post-genomic tools such as the draft sequence information (18), EST Databases (22), microarrays (23)(24)(25), and transgenic techniques (26), Bombyx could be a suitable model for clarifying the genetic basis of body color formation in other insects. Using the newly assembled genome sequence, we have already cloned seven genes required for normal color pattern in Bombyx larvae (9,13,(27)(28)(29)(30). Further studies on Bombyx color mutants will identify novel molecules involved in insect body color patterns.…”
Yellow proteins form a large family in insects. In Drosophila melanogaster, there are 14 yellow genes in the genome. Previous studies have shown that the yellow gene is necessary for normal pigmentation; however, the roles of other yellow genes in body coloration are not known. Here, we provide the first evidence that yellow-e is required for normal body color pattern in insect larvae. In two mutant strains, bts and its allele bts2, of the silkworm Bombyx mori, the larval head cuticle and anal plates are reddish brown instead of the white color found in the wild type. Positional cloning revealed that deletions in the Bombyx homolog of the Drosophila yellow-e gene (Bmyellow-e) were responsible for the bts/bts2 phenotype. Bmyellow-e mRNA was strongly expressed in the trachea, testis, and integument, and expression markedly increased at the molting stages. This profile is quite similar to that of Bmyellow, a regulator of neonatal body color and body markings in Bombyx. Quantitative reverse transcription-PCR analysis showed that Bmyellow-e mRNA was heavily expressed in the integument of the head and tail in which the bts phenotype is observed. The present results suggest that Yellow-e plays a crucial role in the pigmentation process of lepidopteran larvae.Major royal jelly proteins (MRJPs) 2 were initially identified as major constituents of royal jelly; they constitute 80 -90% of total royal jelly proteins, which play a central role in honeybee development (1). The yellow gene family of Drosophila melanogaster is known to encode the MRJP domain-containing protein (2) and to consist of 14 genes (3). The D. melanogaster yellow gene (Dmyellow) determines the degree and pattern of melanization by cooperating with the ebony gene (4). Dmyellow also controls male courtship behavior by its temporal expression in the brain (5). Furthermore, biochemical experiments revealed that the products of two other yellow genes, Dmyellow-f and Dmyellow-f2, have dopachrome-conversion enzyme activity (6). Despite the widespread use of the yellow gene as a visible genetic marker, there is little information regarding the functions of other members of the MRJP/YELLOW protein family in Drosophila and other organisms.Larval color variations are often observed in many lepidopteran insects. About 40 body color mutants have been reported in the silkworm, Bombyx mori (7,8). Recently, two mutants, chocolate (ch) and sooty (so), were characterized molecularly. In the ch mutants, the body color of neonatal larvae and the body markings of older instar larvae are reddish brown instead of normal black. Mutations at the so locus produce smoky larvae and black pupae. Linkage analysis and genomic studies revealed that Bombyx yellow and ebony are the genes responsible for the ch and so mutation, respectively (9). These results suggest that Yellow promotes and Ebony inhibits melanization in Lepidoptera and that melanin-synthesis enzymes play a critical role in the color pattern of lepidopteran larvae.In the bts (brown head and tail spot) body color mutant ...
“…In B. mori , the white colour of larval integument is formed by uric acid accumulation (Hatamura, 1943; Jucci, 1932; Shimizu, 1943). Although uric acid also accumulates in larval integument of B. mandarina (Fujii et al, 2009), regions surrounding banding and spots is darkened by the additional accumulation of unknown yellow pigments (see Xanthus larvae in Fujii et al, 2021).…”
The domesticated silkworm, Bombyx mori, and its wild progenitor, B. mandarina, are extensively studied as a model case of the evolutionary process of domestication. A conspicuous difference between these species is the dramatic reduction in melanin pigmentation in both larval and adult B. mori. Here we evaluate the efficiency of CRISPR/Cas9‐targeted knockouts of pigment‐related genes as a tool to understand their potential contributions to domestication‐associated melanin pigmentation loss in B. mori. To demonstrate the efficacy of targeted knockouts in B. mandarina, we generated a homozygous CRISPR/Cas9‐targeted knockout of yellow‐y. In yellow‐y knockout mutants, black body colour became lighter throughout the larval, pupal and adult stages, confirming a role for this gene in melanin pigment formation. Further, we performed allele‐specific CRISPR/Cas9‐targeted knockouts of the pigment‐related transcription factor, apontic‐like (apt‐like) in B. mori × B. mandarina F1 hybrid individuals which exhibit B. mandarina‐like larval pigmentation. Knockout of the B. mandarina allele of apt‐like in F1 embryos results in white patches on the dorsal integument of larvae, whereas corresponding knockouts of the B. mori allele consistently exhibit normal F1 larval pigmentation. These results demonstrate a contribution of apt‐like to the evolution of reduced melanin pigmentation in B. mori. Together, our results demonstrate the feasibility of CRISPR/Cas9‐targeted knockouts as a tool for understanding the genetic basis of traits associated with B. mori domestication.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
