Erythrocyte pyruvate kinase deficiency mutation identified in multiple breeds of domestic cats.
Erythrocyte pyruvate kinase deficiency mutation identified in multiple breeds of domestic cats.
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DOI：
10.1186/1746-6148-8-207
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发表时间：
2012-10-30
影响因子：
2.6
通讯作者：
Lyons LA
中科院分区：
文献类型：
--
作者：
Grahn RA;Grahn JC;Penedo MC;Helps CR;Lyons LA
红细胞丙酮酸激酶缺乏症(PK缺乏症)是一种遗传性溶血性贫血，已在阿比西尼亚和索马里品种以及随机繁殖的国内短毛猫中发现。这种疾病是由PKLR基因突变引起的，PKLR基因编码调节糖酵解酶丙酮酸激酶(PK)。多种同工酶是通过对PKLR mRNA进行组织特异性差异处理而产生的。PK的紊乱降低了红细胞的寿命，导致贫血。其他体征包括：严重的嗜睡、虚弱、体重减轻、黄疸和腹部肿大。在家猫中，PK缺乏症具有常染色体隐性遗传方式，其发病和临床症状的严重程度具有很高的变异性。序列分析显示，在阿比西尼亚猫和索马里猫中，PKLR基因304位的内含子5单核苷酸多态(SNP)与疾病表型一致。内含子SNP位于第6外显子剪接点的上游53个核苷酸，产生肝脏和血液加工的mRNA，外显子5的3‘端有13个碱基缺失。这种移码突变在第6外显子的第248位氨基酸产生一个终止密码子。在14,179只欧美猫中，代表38个品种的14,179只猫，76只西方随机繁育的猫和111只未知品种的猫，当限制在15个携带一致SNP的群体时，内含子SNP的频率分别为6.31%和9.35%。建议对孟加拉猫、埃及猫、La Perms猫、缅因州浣熊猫、挪威森林猫、萨凡纳猫、西伯利亚猫和新加坡猫进行PK测试，除了阿比西尼亚人和索马里人，以及在Out杂交或开发计划中使用上述品种的任何新品种。
Erythrocyte pyruvate kinase deficiency (PK deficiency) is an inherited hemolytic anemia that has been documented in the Abyssinian and Somali breeds as well as random bred domestic shorthair cats. The disease results from mutations in PKLR, the gene encoding the regulatory glycolytic enzyme pyruvate kinase (PK). Multiple isozymes are produced by tissue-specific differential processing of PKLR mRNA. Perturbation of PK decreases erythrocyte longevity resulting in anemia. Additional signs include: severe lethargy, weakness, weight loss, jaundice, and abdominal enlargement. In domestic cats, PK deficiency has an autosomal recessive mode of inheritance with high variability in onset and severity of clinical symptoms. Sequence analysis of PKLR revealed an intron 5 single nucleotide polymorphism (SNP) at position 304 concordant with the disease phenotype in Abyssinian and Somali cats. Located 53 nucleotides upstream of the exon 6 splice site, cats with this SNP produce liver and blood processed mRNA with a 13 bp deletion at the 3’ end of exon 5. The frame-shift mutation creates a stop codon at amino acid position 248 in exon 6. The frequency of the intronic SNP in 14,179 American and European cats representing 38 breeds, 76 western random bred cats and 111 cats of unknown breed is 6.31% and 9.35% when restricted to the 15 groups carrying the concordant SNP. PK testing is recommended for Bengals, Egyptian Maus, La Perms, Maine Coon cats, Norwegian Forest cats, Savannahs, Siberians, and Singapuras, in addition to Abyssinians and Somalis as well an any new breeds using the afore mentioned breeds in out crossing or development programs.
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影响因子：
3.3
作者：
Helps, Chris R.;Tasker, Severine;Gruffydd-Jones, Timothy J.
通讯作者：
Gruffydd-Jones, Timothy J.
影响因子：
2.6
作者：
Gultekin GI;Raj K;Foureman P;Lehman S;Manhart K;Abdulmalik O;Giger U
通讯作者：
Giger U
影响因子：
3.9
作者：
Coutinho, G;Xie, JY;Gatti, RA
通讯作者：
Gatti, RA
影响因子：
64.8
作者：
MARIE, J;SIMON, MP;KAHN, A
通讯作者：
KAHN, A
影响因子：
3.5
作者：
Kedar, P.;Hamada, T.;Colah, R.
通讯作者：
Colah, R.