Identification of the place of origin of mutations through surnames.

The estimate of the incidence of a disease with autosomal recessive heredity in an area can be obtained when the level of inbreeding of that area is known. Dahlberg's or Barrai's more general formulas allowed to obtain estimates of the gene frequency for Werner syndrome, phenylketonuria, Friedreich ataxia and cystic fibrosis in Italy, using the records of consanguineous marriages occurred between 1911 and 1964, subdivided in five year periods and among the 92 Italian provinces. The same data on consanguinity and the information derived from the Italian register of the ataxia-telangiectasia (AT), referring to 72 families and 91 probands, allowed the estimate of the gene frequency of this recessive syndrome that exhibits neurological and immunological alterations and for which heterozygotes develop a high risk of cancer. Since the frequency of Italian consanguineous marriages showed a high spatial heterogeneity, the correctness of the estimate of the gene frequency and, hence, of the heterozygote frequency, depends on the accurate attribution of the area of origin of the patients' family. The estimate of the disease frequency, obtained with a geographical distribution of the affected based on the father's birthplace, was q=0.01188, corresponding to a q2 value of 1/7090 and to a general heterozygote frequency of 2.34% (7). Since the father's birthplace may not always correspond to the ancient place of origin of the family, i.e. the probable place where the mutation arose, the correctness of the geographical attribution was verified using surname data which, for their characteristic of genetic markers, can identify genetically homogeneous areas. Surnames of the probands' parents and maternal and paternal grandparents were extracted from the register of AT patients and the probable place of origin of each family could be assigned by the comparison with a data bank of the Italian surnames (still incomplete). For 51 families the information obtained on the basis of the surname distribution analysis allowed a "certain" localization of the family in a region because all or at least one ancestor from the paternal and one from the maternal lineage came from the same region; of these families, 41 confirmed the localization derived from the father's birthplace. For 16 families, on the contrary, the information from surnames allowed a "probable" localization because the members of the paternal and maternal lineages came from different regions, one of which, however, corresponded to the father's birthplace. For 5 families surnames didn't allow an identification of the place of origin. From the estimate of the gene frequency obtained with the new geographical re-distribution of each family a value of q2=1/5510 and a heterozygote frequency of 2.66% were obtained. The use of surnames, therefore, often seems to allow a correct identification of the place of origin of individuals, beyond the present geographical distribution which is the result of modern migrations.