Treacy E, Byck S, Clow C, Scriver C R
DeBelle Laboratory, McGill University-Montreal Children's Hospital Research Institute, Canada.
Eur J Hum Genet. 1993;1(3):220-8. doi: 10.1159/000472415.
We analyzed mutations, RFLP haplotypes (H), and a VNTR polymorphism at the phenylalanine hydroxylase locus (PAH) in 12 French-Canadian patients with phenylketonuria (PKU) from the eastern region of Quebec province and 13 non-French-Canadian PKU patients from the Montreal region. There were 10 different mutation/H/VNTR haplotype combinations on the 50 PKU chromosomes: one set of 5 and another of 8 accounted for 88 and 77% of these chromosomes in the French-Canadian and non-French-Canadian patients, respectively. The differences in PKU haplotypes between the two groups of probands reflect the different histories of the two populations. Three PKU haplotype combinations were shared by the two groups: IVS12nt1:H-3:VNTR-8, I65T:H-9:VNTR-8, and R408W:H-1:VNTR-8. The IVS12nt1 mutation (18% of the total sample) is prevalent in northern Europeans. The I65T-H-9 and R408W:H-1 haplotypes have seldom been reported in Europeans but when encountered tend to be found in northwestern regions. The R408W mutation is usually on H-2 in Europeans. In Quebec the R408W:H-1 and I65T:H-9 haplotypes accounted for 20% of PKU chromosomes, clustered in two geographic regions, and in every family where they occurred an Irish or Scottish ('Celtic') ancestor could be inferred. We propose that I65T:H-9:VNTR-8 and R408W:H-1:VNTR-8 chromosomes are markers for a diaspora of 'Celtic' descendants. Our findings predict the distributions of these unusual PKU haplotypes in contemporary Europeans.
我们分析了来自魁北克省东部地区的12名法裔加拿大苯丙酮尿症（PKU）患者以及来自蒙特利尔地区的13名非法裔加拿大PKU患者的苯丙氨酸羟化酶基因座（PAH）的突变、限制性片段长度多态性单倍型（H）和可变数目串联重复多态性。在50条PKU染色体上有10种不同的突变/H/可变数目串联重复单倍型组合：一组5种和另一组8种分别占法裔加拿大患者和非法裔加拿大患者这些染色体的88%和77%。两组先证者的PKU单倍型差异反映了两个人群的不同历史。两组共有三种PKU单倍型组合：内含子12第1位核苷酸突变（IVS12nt1）:H-3:可变数目串联重复序列-8（VNTR-8）、I65T:H-9:VNTR-8和R408W:H-1:VNTR-8。IVS12nt1突变（占总样本的18%）在北欧人中很常见。I65T-H-9和R408W:H-1单倍型在欧洲人中很少被报道，但一旦出现往往在西北地区被发现。R408W突变在欧洲人中通常位于H-2上。在魁北克，R408W:H-1和I65T:H-9单倍型占PKU染色体的20%，聚集在两个地理区域，并且在它们出现的每个家族中都可以推断出有爱尔兰或苏格兰（“凯尔特”）祖先。我们提出I65T:H-9:VNTR-8和R408W:H-1:VNTR-8染色体是“凯尔特”后裔散居的标记。我们的研究结果预测了这些不寻常的PKU单倍型在当代欧洲人中的分布情况。
