<Research - Institute of Genetics - Human Genetics and Carcinogenesis Unit - Laboratory of Molecular Human Genetics

István RASKÓ
Professor emeritus, Principal Investigator

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Anita KÁITY-SZÉCSÉNYI Staff Scientist
Mária RADÓNÉ DUDÁS Technician

GENOMIC APPROACHES IN STUDIES OF HUMAN DISEASE AND POPULATION ORIGINS

During the last several years it has become clear that ancient DNA (aDNA) is preserved in archeological specimens, but usually in tiny amounts, seriously damaged, often contaminated with inhibitory substances from the soil or with fungal or bacterial DNA. Ancient DNA offers applications in genetic studies of ancient human populations and in reconstructing human population history.


Archeological genetics

Mitochondrial DNA (mtDNA) is used in aDNA studies to trace maternal lineages, on account of its high copy number and the lack of recombination. Y chromosomal non-recombining regional polymorphisms, on the other hand, are useful in following paternal inheritance. These two tools are routinely used in human phylogeographic studies. Human mtDNA D-loop and Y chromosomal mutations have accumulated sequentially along radiating maternal and paternal lineages during and after the process of human colonization of different geographical regions of the world. Their analysis enables the study of the genetic traces of migration and the admixtures of different human communities and helps in estimating the degree of relationships within and between populations. An efficient method was developed in our laboratory to isolate PCR-amplifiable DNA from ancient bones. The mitochondrial and Y chromosomal archeogenetic map of the Carpatian basin at the time of the arrival of the Hungarian tribes in the 10th -11th centuries has been established. PCR-amplifiable aDNA was isolated from bones originating from archeologically characterized burial sites in Hungary. After sequencing, the mtDNA and Y chromosome haplotypes and the monophyletic clades (haplogroups) which the samples belong to were determined. These data and those from modern Hungarian and Secler samples were used to assign the relationships between the samples and the sequences of 153 worldwide populations in our database. Recently lactose tolerance, a trait which has evolved as a result of cultural selection is being studied in recent and ancient Hungarian populations. In compliance with ancient Hungarian burial customs, noble Hungarians in the 10th -11th centuries were buried with their horses. The determination of the genetic relationships of these animals by means of mitochondrial DNA analysis is in progress.



Figure 1. From bone to mitochondrial sequences


Interaction of genetic pathways in nerve specific differentiation

We have previously established that a gene, which belongs to the forming gene family is participating in the induction of nerve specific differentiation in mouse teratocarcinoma P19 cell line. Studies are in progress to understand the underlying genetic interactions.



Selected publications

Raskó I. and Downes, C.S. (1994). Genes in Medicine. Molecular biology and human genetic disorders. Chapman & Hall London.

Kalmár, T., Bachrati, C., Marcsik, A. and Raskó, I. (2000). A simple and efficient method for PCR amplifiable DNA extraction from ancient bones. Nucl. Acids Res. 28: e67.

Bogácsi-Szabó, E., Kalmár, T., Csányi, B., Tömöry,Gy., Czibula, Á., Priskin, K., Horváth, F., Downes,C.S. and Raskó, I. (2005). Mitochondrial DNA of Ancient Cumanians: Culturally Asian Steppe Nomadic Immigrants with Substantially More Western Eurasian Mitochondrial DNA Lineages. Human Biology 77: 639-662.

Tömöry, G., Csányi, B., Bogácsi-Szabó, E., Kalmár, T., Czibula, Á., Csősz A., Priskin, K., Mende, B., Lango, P., Downes, C.S. and Rasko, I. (2007). Comparison of maternal lineage and biogeographic analyses of ancient and modern Hungarian populations. Am. J. Phys. Anthropol. 134: 354-368.

Priskin, K., Tömöry, G., Bogácsi-Szabó, E., Csányi, B., Vörös I. and Raskó, I. (2007). Mitochondrial DNA control region analysis of a late Neolithic aurochs (Bos primigenius Boj. 1827.) from the Carpathian Basin. Acta Biol. Hung. 58: 131-137.

Csányi, B., Bogácsi-Szabó, E., Tömöry, G., Czibula, Á., Priskin, Csősz, A., Mende, B., Lango, P., Csete, K., Zsolnai, A., Conant, E.K., Downes,C.S. and Raskó, I. (2008). Y-chromosome analysis of ancient Hungarian and two modern Hungarian-speaking populations from the Carpathian Basin. Ann. Hum. Genet. 72: 519-534.

Matusek, T., Gombos, R., Szécsényi A., Sánchez-Soriano, N., Czibula, Á., Pataki C., Gedai, A., Prokop, A., Raskó I. and Mihály, J. (2008). Formin proteins of the DAAM subfamily play a role during axon growth. J. Neurosci. 28: 13310-13319.

Nagy, D., Bogácsi Szabó, E., Várkonyi, Á., Csányi, B., Czibula, Á., Bede, O., Tari, B. and Raskó, I. (2009). Prevalence of adult-type hypolactasia as diagnosed with genetic and lactose hydrogen breath tests in Hungarians. Eur. J. Clin. Nutr. 63: 909–912.