Single Nucleotide Polymorphisms Associated with AA-Amyloidosis in Siamese and Oriental Shorthair Cats.

AA-amyloidosis in Siamese and Oriental shorthair cats is a lethal condition in which amyloid deposits accumulate systemically, especially in the liver and the thyroid gland. The age at death of affected cats varies between one and seven years. A previous study indicated a complex mode of inheritance involving a major locus. In the present study, we performed a multi-locus genome-wide association study (GWAS) using five methods (mrMLM, FASTmrMLM, FASTmrEMMA, pLARmEB and ISIS EM-BLASSO) to identify variants associated with AA-amyloidosis in Siamese/Oriental cats. We genotyped 20 affected mixed Siamese/Oriental cats from a cattery and 48 healthy controls from the same breeds using the Illumina Infinium Feline 63 K iSelect DNA array. The multi-locus GWAS revealed eight significantly associated single nucleotide polymorphisms (SNPs) on FCA A1, D1, D2 and D3. The genomic regions harboring these SNPs contain 55 genes, of which 3 are associated with amyloidosis in humans or mice. One of these genes is SAA1, which encodes for a member of the Serum Amyloid A family, the precursor protein of Amyloid A, and a mutation in the promotor of this gene causes hereditary AA-amyloidosis in humans. These results provide novel knowledge regarding the complex genetic background of hereditary AA-amyloidosis in Siamese/Oriental cats and, therefore, contribute to future genomic studies of this disease in cats.

Novel Mutation in the Feline NPC2 Gene in Cats with Niemann-Pick Disease.

Niemann-Pick disease (NP) type C is an autosomal, recessive, and inherited neurovisceral genetic disorder characterized by the accumulation of unesterified cholesterol and glycolipids in cellular lysosomes and late endosomes, with a wide spectrum of clinical phenotypes. This study aimed to determine the molecular genetic alterations in two cases of felines with NP in Japan, a Siamese cat in 1989 and a Japanese domestic (JD) cat in 1998. Sanger sequencing was performed on 25 exons of the feline NPC1 gene and 4 exons of the feline NPC2 gene, using genomic DNA extracted from paraffin-embedded tissue specimens. The sequenced exons were compared with reference sequences retrieved from the GenBank database. The identified mutations and alterations were then analyzed using different prediction algorithms. No pathogenic mutations were found in feline NPC1; however, c.376G>A (p.V126M) was identified as a pathogenic mutation in the NPC2 gene. The Siamese cat was found to be homozygous for this mutation. The JD cat was heterozygous for the same mutation, but no other exonic NPC2 mutation was found. Furthermore, the JD cat had a homozygous splice variant (c.364-4C>T) in the NPC2 gene, which is not known to be associated with this disease. The NPC2:c.376G>A (p.V126M) mutation is the second reported pathogenic mutation in the feline NPC2 gene that may be present in the Japanese cat population.

Transient skin and fur color change after trichotomy of the sacrococcygeal region for epidural anesthesia in a domestic cat (Felis catus) / Mudança transitória da cor da pele e pelo após tricotomia da região sacrococcígea para anestesia epidural em gata doméstica (Felis catus)

A clinical case in which skin and hair color change occurred after sacrococcygeal epidural anesthesia in a nine-month-old Siamese cross queen undergoing ovariohysterectomy (OHE) is described. Six weeks after surgery, during a re-check, it was noted that in the sacrococcygeal region the color of the skin and new hair growth was dark with a color comparable to the color present on the body extremities (muzzle, pinnae, legs, and tail). The skin and new hair growth of the shaved abdomen presented a standard color. The key enzyme of the melanogenic pathway in mammals is tyrosinase (TYR), and the Siamese temperature-sensitive phenotype is the result of genetic mutations that makes TYR function thermolabile. The activity of TYR in these cats is limited to the extremities where the temperature is lower while pigment production is impaired in the other body areas. The trichotomy of the sacrococcygeal region performed during wintertime in an outdoor cat was probably the trigger for increased activity of TYR in this area promoting pigment production. The absence of the same alterations in the abdominal area may be justified by less exposure of that region to the external environment, as well as to the feline habits of sedentarism, that avoid significant cooling in these regions. This report highlights the importance of taking this type of occurrence into account when performing an epidural in the Siamese cat breed. Also, to avoid skin color change in this breed, the authors recommend a midline abdominal instead of a flank approach to perform OHE.(AU)

Descreve-se um caso clínico no qual ocorreu mudança na cor da pele e do pelo após anestesia epidural sacrococcígea numa gata cruzada de raça Siamês de nove meses submetida à ovariohisterectomia (OVH). Seis semanas após a cirurgia, durante uma avaliação pós-operatória, notou-se que na região sacrococcígea, a cor da pele e o crescimento do pelo apresentavam uma cor escura, comparável à das extremidades do corpo (face, orelhas, membros e cauda). A pele e o crescimento do pelo do abdómen, que também havia sido tosquiado, apresentavam uma cor padrão. A enzima chave da via melanogênica em mamíferos é a tirosinase (TYR) e o fenótipo siamês sensível à temperatura é o resultado de mutações genéticas que tornam a função TYR termolábil. A atividade da TYR nestes gatos é limitada às extremidades onde a temperatura é mais baixa, enquanto a produção de pigmento é prejudicada em outras áreas do corpo. A tricotomia da região sacrococcígea realizada durante o inverno nesta gata com acesso livre ao ambiente externo, provavelmente determinou um aumento da atividade da TYR nesta área, promovendo a produção de pigmento. A ausência das mesmas alterações na região abdominal pode ser justificada pela menor exposição desta área do corpo ao ambiente externo, também devido aos hábitos felinos de sedentarismo, que evitam resfriamento significativo nestas regiões. Este relato destaca a importância de se levar em consideração a possibilidade deste tipo de ocorrência quando da realização de uma anestesia epidural nesta raça de gatos. Além disso, os autores recomendam uma abordagem abdominal na linha média ao invés de uma abordagem de flanco para realizar a OVH nesta raça, a fim de evitar a alteração da cor da pele.(AU)

Rainer W. Guillery and the genetic analysis of brain development.

Ray Guillery had broad research interests that spanned cellular neuroanatomy, but was perhaps best known for his investigation of the connectivity and function of the thalamus, especially the visual pathways. His work on the genetics of abnormal vision in albino mammals served as an early paradigm for genetic approaches for studying brain connectivity of complex species in general, and remains of major relevance today. This work, especially on the Siamese cat, illustrates the complex relationship between genotype and physiology of cerebral cortical circuits, and anticipated many of the issues underlying the imperfect relationship between genes, circuits, and behavior in mammalian species including human. This review also briefly summarizes studies from our own lab inspired by Ray Guillery's legacy that continues to explore the relationship between genes, structure, and behavior in human cerebral cortex.