{"id":107086,"date":"2025-05-16T19:38:10","date_gmt":"2025-05-16T19:38:10","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/107086\/"},"modified":"2025-05-16T19:38:10","modified_gmt":"2025-05-16T19:38:10","slug":"researchers-identify-genetic-mutation-responsible-for-orange-coat-in-domestic-cats","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/107086\/","title":{"rendered":"Researchers Identify Genetic Mutation Responsible for Orange Coat in Domestic Cats"},"content":{"rendered":"

This mutation is located in the Rho GTPase Activating Protein 36<\/a> (Arhgap36) gene and appears to occur in no other mammal, according to a research team led by Stanford University School of Medicine scientists.<\/strong><\/p>\n

\"The<\/a><\/p>\n

The sex-linked orange mutation in domestic cats causes variegated patches of reddish\/yellow hair and is a defining signature of random X inactivation in female tortoiseshell and calico cats; unlike the situation for most coat color genes, there is no apparent homolog for sex-linked orange in other mammals; Kaelin et al. show that sex-linked orange is caused by a 5-kb deletion that leads to ectopic and melanocyte-specific expression of the Arhgap36 gene. Image credit: Kaelin et al., doi: 10.1016\/j.cub.2025.04.055.<\/p>\n

Lots of mammals come in shades of orange \u2014 think tigers, golden retrievers, orangutans and red-headed humans \u2014 but only in domestic cats (Felis silvestris catus)<\/a> is orange coloration linked to sex, appearing much more often in males.<\/p>\n

\u201cIn a number of species that have yellow or orange pigment, those mutations almost exclusively occur in one of two genes, and neither of those genes are sex-linked,\u201d said Dr. Christopher Kaelin, a researcher at Stanford University School of Medicine and HudsonAlpha Institute for Biotechnology.<\/p>\n

While scientists have pinpointed the typical mutations that induce pigment cells in the skin to produce yellow or orange pigment instead of the default brown or black, they had only a rough idea of where to find the corresponding mutation in cats.<\/p>\n

They knew from the preponderance of male orange cats that the mutation \u2014 dubbed sex-linked orange \u2014 was somewhere on the X chromosome.<\/p>\n

Any male cat with sex-linked orange will be entirely orange, but a female cat needs to inherit sex-linked orange on both X chromosomes to be entirely orange \u2014 a less likely occurrence.<\/p>\n

Female cats with one copy of sex-linked orange appear partially orange \u2014 with a mottled pattern known as tortoiseshell, or with patches of orange, black and white known as calico.<\/p>\n

That\u2019s due to a genetic phenomenon in females, called random X inactivation, in which one X chromosome is inactivated in each cell.<\/p>\n

The result is a mosaic of pigment cells, some that express sex-linked orange and others that do not.<\/p>\n

\u201cIt\u2019s a genetic exception that was noticed over a hundred years ago,\u201d Dr. Kaelin said.<\/p>\n

\u201cIt\u2019s really that comparative genetic puzzle that motivated our interest in sex-linked orange.\u201d<\/p>\n

Building on a prior study that had begun to narrow down the region of the X chromosome containing the mutation, Dr. Kaelin and his colleagues zeroed in on sex-linked orange using a step-by-step process.<\/p>\n

\u201cOur ability to do this has been enabled by the development of genomic resources for the cat that have become available in just the last 5 or 10 years,\u201d Dr. Kaelin said.<\/p>\n

\u201cThat includes the complete sequenced genomes of a wide assortment of cats.\u201d<\/p>\n

The researchers also collected DNA samples from cats at spay and neuter clinics.<\/p>\n

First, they looked for variants on the X chromosome shared by male orange cats and found 51 candidates.<\/p>\n

They eliminated 48 of these, as they were also found in some non-orange cats.<\/p>\n

Of the three remaining variants, one stood out as likely having a role in gene regulation: it was a small deletion that increased the activity of a nearby gene known as Arhgap36.<\/p>\n

\u201cAt the time we found it, the Arhgap36 gene had no connection to pigmentation,\u201d Dr. Kaelin said.<\/p>\n

The gene, which is highly conserved in mammalian species, was being studied by researchers in cancer and developmental biology.<\/p>\n

Arhgap36 is normally expressed in neuroendocrine tissues, where overexpression can lead to tumors. It was not known to do anything in pigment cells.<\/p>\n

Except, Dr. Kaelin and colleagues discovered, in pumpkin-colored cats.<\/p>\n

\u201cArghap36 is not expressed in mouse pigment cells, in human pigment cells or in cat pigment cells from non-orange cats,\u201d Dr. Kaelin said.<\/p>\n

\u201cThe mutation in orange cats seems to turn on Arghap36 expression in a cell type, the pigment cell, where it\u2019s not normally expressed.\u201d<\/p>\n

This rogue expression in pigment cells inhibits an intermediate step of a well-known molecular pathway that controls coat color \u2014 the same one that operates in other orange-shaded mammals.<\/p>\n

In those species, typical orange mutations disrupt an earlier step in that pathway; in cats, sex-linked orange disrupts a later step.<\/p>\n

\u201cCertainly, this is a very unusual mechanism where you get misexpression of a gene in a specific cell type,\u201d Dr. Kaelin said.<\/p>\n

The team\u2019s discovery is described in a paper<\/a> published this week in the journal Current Biology.<\/p>\n

_____<\/p>\n

Christopher B. Kaelin et al. Molecular and genetic characterization of sex-linked orange coat color in the domestic cat. Current Biology, published online May 15, 2025; doi: 10.1016\/j.cub.2025.04.055<\/p>\n","protected":false},"excerpt":{"rendered":"This mutation is located in the Rho GTPase Activating Protein 36 (Arhgap36) gene and appears to occur in…\n","protected":false},"author":2,"featured_media":107087,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3846],"tags":[49010,28471,49011,24715,49012,3908,49013,49014,49015,49016,49017,3909,267,3895,49018,26423,49019,70,16,15,49020,49021],"class_list":{"0":"post-107086","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-arhgap36","9":"tag-cat","10":"tag-chromosome","11":"tag-color","12":"tag-coloration","13":"tag-dna","14":"tag-felidae","15":"tag-felis","16":"tag-felis-catus","17":"tag-felis-silvestris","18":"tag-fur","19":"tag-gene","20":"tag-genetics","21":"tag-genome","22":"tag-mammal","23":"tag-mutation","24":"tag-pigment","25":"tag-science","26":"tag-uk","27":"tag-united-kingdom","28":"tag-x-chromosome","29":"tag-y-chromosome"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/114519206280662934","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/107086","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=107086"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/107086\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/107087"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=107086"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=107086"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=107086"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}