Dominant Blauwe Ogen NEW

@article{pmid38869246,

title = {PAX3 haploinsufficiency in Maine Coon cats with dominant blue eyes and hearing loss resembling the human Waardenburg syndrome},

author = {Gabriela Rudd Garces and Daniela Farke and Martin J Schmidt and Anna Letko and Katja Schirl and Marie Abitbol and Tosso Leeb and Leslie A Lyons and Gesine Lühken},

doi = {10.1093/g3journal/jkae131},

issn = {2160-1836},

year  = {2024},

date = {2024-09-01},

urldate = {2024-09-01},

journal = {G3 (Bethesda)},

volume = {14},

number = {9},

abstract = {This study investigated the dominant blue eyes (DBE) trait linked to hearing impairment and variable white spotting in Maine Coon cats. Fifty-eight animals descending from 2 different DBE lineages, the Dutch and the Topaz lines, were sampled. They comprised 48 cats from the Dutch bloodline, including 9 green-eyed and 31 blue-eyed cats, with some individuals exhibiting signs of deafness, and 8 stillborn kittens. Samples from the Topaz lineage included 10 blue-eyed animals. A brainstem auditory evoked response test revealed a reduced to absent response to auditory stimuli and absent physiological waveforms in all of the 8 examined DBE animals. We sequenced the genome of 2 affected cats from the Dutch line and searched for variants in 19 candidate genes for the human Waardenburg syndrome and pigmentary disorders. This search yielded 9 private protein-changing candidate variants in the genes PAX3, EDN3, KIT, OCA2, SLC24A5, HERC2, and TYRP1. The genotype-phenotype cosegregation was observed for the PAX3 variant within all animals from the Dutch lineage. The mutant allele was absent from 461 control genomes and 241 additionally genotyped green-eyed Maine Coons. We considered the PAX3 variant as the most plausible candidate-a heterozygous nonsense single base pair substitution in exon 6 of PAX3 (NC_051841.1:g.205,787,310G>A, XM_019838731.3:c.937C>T, XP_019694290.1:p.Gln313*), predicted to result in a premature stop codon. PAX3 variants cause auditory-pigmentary syndrome in humans, horses, and mice. Together with the comparative data from other species, our findings strongly suggest PAX3:c.937C>T (OMIA:001688-9685) as the most likely candidate variant for the DBE, deafness, and minimal white spotting in the Maine Coon Dutch line. Finally, we propose the designation of DBERE (Rociri Elvis Dominant Blue Eyes) allele in the domestic cat.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38644700,

title = {A PAX3 insertion in the Celestial breed and certain feline breeding lines with dominant blue eyes},

author = {Marie Abitbol and Alice Couronné and Caroline Dufaure de Citres and Vincent Gache},

doi = {10.1111/age.13433},

issn = {1365-2052},

year  = {2024},

date = {2024-08-01},

urldate = {2024-08-01},

journal = {Anim Genet},

volume = {55},

number = {4},

pages = {670--675},

abstract = {During the last 60 years many inherited traits in domestic outbred cats were selected and retained giving birth to new breeds characterised by singular coat or morphological phenotypes. Among them, minimal white spotting associated with blue eyes was selected by feline breeders to create the Altai, Topaz, and Celestial breeds. Various established breeds also introduced this trait in their lineages. The trait, that was confirmed as autosomal dominant by breeding data, was first described in domestic cats from Kazakhstan and Russia, in British shorthair and British longhair from Russia, and in Maine Coon cats from the Netherlands, suggesting different founding effects. Using a genome-wide association study we identified a single region on chromosome C1 that was associated with the minimal white spotting and blue eyes phenotype (also called DBE by breeders for dominant blue eyes) in the French Celestial breed. Within that region we identified Paired Box 3 (PAX3) as the strongest candidate gene, since PAX3 is a key regulator of MITF (Melanocyte-Inducing Transcription Factor) and PAX3 variants have been previously identified in various species showing white spotting with or without blue eyes including the mouse and the horse. Whole genome sequencing of a Celestial cat revealed an endogenous retrovirus LTR (long terminal repeat) insertion within PAX3 intron 4 known to contain regulatory sequences (conserved non-coding element [CNE]) involved in PAX3 expression. The insertion is in the vicinity of CNE2 and CNE3. All 52 Celestial and Celestial-mixed cats with a DBE phenotype presented the insertion, that was absent in their 22 non-DBE littermates and in 87 non-DBE cats from various breeds. The outbred Celestial founder was also heterozygous for the insertion. Additionally, the variant was found in nine DBE Maine Coon cats related to the Celestial founder and four DBE Siberian cats with an uncertain origin. Segregation of the variant in the Celestial breed is consistent with dominant inheritance and does not appear to be associated with deafness. We propose that this NC_018730.3:g.206974029_206974030insN[395] variant represents the DBE (Celestial Dominant Blue Eyes) allele in the domestic cat.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38997957,

title = {Different Founding Effects Underlie Dominant Blue Eyes (DBE) in the Domestic Cat},

author = {Marie Abitbol and Caroline Dufaure de Citres and Gabriela Rudd Garces and Gesine Lühken and Leslie A Lyons and Vincent Gache},

doi = {10.3390/ani14131845},

issn = {2076-2615},

year  = {2024},

date = {2024-06-01},

urldate = {2024-06-01},

journal = {Animals (Basel)},

volume = {14},

number = {13},

abstract = {During the last twenty years, minimal white spotting associated with blue eyes was selected by feline breeders to create the Altai, Topaz, and Celestial breeds. Additionally, certain breeders introduced this trait in their lineages of purebred cats. The trait has been called "dominant blue eyes (DBE)" and was confirmed to be autosomal dominant in all lineages. DBE was initially described in outbred cats from Kazakhstan and Russia and in two purebred lineages of British cats from Russia, as well as in Dutch Maine Coon cats, suggesting different founding effects. We have previously identified two variants in the  gene associated with DBE in Maine Coon and Celestial cats; however, the presence of an underlying variant remains undetermined in other DBE breeding lines. Using a genome-wide association study, we identified a single region on chromosome C1 that was associated with DBE in British cats. Within that region, we identified  as the strongest candidate gene. Whole-genome sequencing of a DBE cat revealed an RD-114 retrovirus LTR (long terminal repeat) insertion within  intron 4 (namely NC_018730.3:g.206975776_206975777insN[433]) known to contain regulatory sequences. Using a panel of 117 DBE cats, we showed that this variant was fully associated with DBE in two British lineages, in Altai cats, and in some other DBE lineages. We propose that this NC_018730.3:g.206975776_206975777insN[433] variant represents the  () allele in the domestic cat. Finally, we genotyped DBE cats from 14 lineages for the three  variants and showed that they were not present in four lineages, confirming genetic heterogeneity of the DBE trait in the domestic cat.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}