L Luca Cavalli-Sforza

Stanford Medicine, Stanford, California, United States

Are you L Luca Cavalli-Sforza?

Claim your profile

Publications (36)352.2 Total impact

  • Source
    Christopher A Edmonds, Anita S Lillie, L Luca Cavalli-Sforza
    [Show abstract] [Hide abstract]
    ABSTRACT: The ability to infer the time and place of origin of a mutation can be very useful when reconstructing the evolutionary histories of populations and species. We use forward computer simulations of population growth, migration, and mutation in an analysis of an expanding population with a wave front that advances at a constant slow rate. A pronounced founder effect can be observed among mutations arising in this wave front where extreme population bottlenecks arise and are followed by major population growth. A fraction of mutations travel with the wave front and generate mutant populations that are on average much larger than those that remain stationary. Analysis of the diffusion of these mutants makes it possible to reconstruct migratory trajectories during population expansions, thus helping us better understand observed patterns in the evolution of species such as modern humans. Examination of some historical data supports our model.
    Proceedings of the National Academy of Sciences 02/2004; 101(4):975-9. · 9.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Analysis of 89 biallelic polymorphisms in 523 Turkish Y chromosomes revealed 52 distinct haplotypes with considerable haplogroup substructure, as exemplified by their respective levels of accumulated diversity at ten short tandem repeat (STR) loci. The major components (haplogroups E3b, G, J, I, L, N, K2, and R1; 94.1%) are shared with European and neighboring Near Eastern populations and contrast with only a minor share of haplogroups related to Central Asian (C, Q and O; 3.4%), Indian (H, R2; 1.5%) and African (A, E3*, E3a; 1%) affinity. The expansion times for 20 haplogroup assemblages was estimated from associated STR diversity. This comprehensive characterization of Y-chromosome heritage addresses many multifaceted aspects of Anatolian prehistory, including: (1) the most frequent haplogroup, J, splits into two sub-clades, one of which (J2) shows decreasing variances with increasing latitude, compatible with a northward expansion; (2) haplogroups G1 and L show affinities with south Caucasus populations in their geographic distribution as well as STR motifs; (3) frequency of haplogroup I, which originated in Europe, declines with increasing longitude, indicating gene flow arriving from Europe; (4) conversely, haplogroup G2 radiates towards Europe; (5) haplogroup E3b3 displays a latitudinal correlation with decreasing frequency northward; (6) haplogroup R1b3 emanates from Turkey towards Southeast Europe and Caucasia and; (7) high resolution SNP analysis provides evidence of a detectable yet weak signal (<9%) of recent paternal gene flow from Central Asia. The variety of Turkish haplotypes is witness to Turkey being both an important source and recipient of gene flow.
    Human Genetics 02/2004; 114(2):127-48. · 4.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Allelic frequencies of 182 tri- and tetra-autosomal microsatellites were used to examine phylogenetic relationships among 19 extant human populations. In particular, because the languages of the Basques and Hunza Burusho have been suggested to have an ancient relationship, this study sought to explore the genetic relationship between these two major language isolate populations and to compare them with other human populations. The work presented here shows that the microsatellite allelic diversity and the number of unique alleles were highest in sub-Saharan Africans. Neighbor-joining trees based on genetic distances and principal component analyses separated populations from different continents, and are consistent with an African origin for modern humans. For the first time, with biparentally transmitted markers, the microsatellite tree also shows that the San are the first branch of the human tree before the branch leading to all other Africans. In contrast to an earlier study, these results provided no evidence of a genetic relationship among the two language isolate groups. Genetic relationships, as ascertained by these microsatellites, are dictated primarily by geographic proximity rather than by remote linguistic origin, Mantel test, R(0) = 0.484, g = 3.802 (critical g value = 1.645; P = 0.05).
    American Journal of Physical Anthropology 12/2003; 122(3):259-68. · 2.51 Impact Factor
  • Source
    L Luca Cavalli-Sforza, Marcus W Feldman
    [Show abstract] [Hide abstract]
    ABSTRACT: The past decade of advances in molecular genetic technology has heralded a new era for all evolutionary studies, but especially the science of human evolution. Data on various kinds of DNA variation in human populations have rapidly accumulated. There is increasing recognition of the importance of this variation for medicine and developmental biology and for understanding the history of our species. Haploid markers from mitochondrial DNA and the Y chromosome have proven invaluable for generating a standard model for evolution of modern humans. Conclusions from earlier research on protein polymorphisms have been generally supported by more sophisticated DNA analysis. Co-evolution of genes with language and some slowly evolving cultural traits, together with the genetic evolution of commensals and parasites that have accompanied modern humans in their expansion from Africa to the other continents, supports and supplements the standard model of genetic evolution. The advances in our understanding of the evolutionary history of humans attests to the advantages of multidisciplinary research.
    Nature Genetics 04/2003; 33 Suppl:266-75. · 29.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The genetic composition of the Norwegian population was investigated by analysing polymorphisms associated with both the mitochondrial DNA (mtDNA) and Y chromosome loci in a sample of 74 Norwegian males. The combination of their uniparental mode of inheritance and the absence of recombination make these haplotypic stretches of DNA the tools of choice in evaluating the different components of a population's gene pool. The sequencing of the Dloop and two diagnostic RFLPs (AluI 7025 and HinfI at 12 308) allowed us to classify the mtDNA molecules in 10 previously described groups. As for the Y chromosome the combination of binary markers and microsatellites allowed us to compare our results to those obtained elsewhere in Europe. Both mtDNA and Y chromosome polymorphisms showed a noticeable genetic affinity between Norwegians and central Europeans, especially Germans. When the phylogeographic analysis of the Y chromosome haplotypes was attempted some interesting clues on the peopling of Norway emerged. Although Y chromosome binary and microsatellite data indicate that 80% of the haplotypes are closely related to Central and western Europeans, the remainder share a unique binary marker (M17) common in eastern Europeans with informative microsatellite haplotypes suggesting a different demographic history. Other minor genetic influences on the Norwegian population from Uralic speakers and Mediterranean populations were also highlighted.
    European Journal of HumanGenetics 10/2002; 10(9):521-9. · 4.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We study a general class of nonlinear macroscopic evolution equations with "transport" and "reaction" terms which describe the dynamics of a species of moving individuals (atoms, molecules, quasiparticles, organisms, etc.). We consider that two types of individuals exist, "not marked" and "marked," respectively. We assume that the concentrations of both types of individuals are measurable and that they obey a neutrality condition, that is, the kinetic and transport properties of the "not marked" and "marked" individuals are identical. We suggest a response experiment, which consists in varying the fraction of "marked" individuals with the preservation of total fluxes, and show that the response of the system can be represented by a linear superposition law even though the underlying dynamics of the system is in general highly nonlinear. The linear response law is valid even for large perturbations and is not the result of a linearization procedure but rather a necessary consequence of the neutrality condition. First, we apply the response theorem to chemical kinetics, where the "marked species" is a molecule labeled with a radioactive isotope and there is no kinetic isotope effect. The susceptibility function of the response law can be related to the reaction mechanism of the process. Secondly we study the geographical distribution of the nonrecurrent, nonreversible neutral mutations of the nonrecombining portion of the Y chromosome from human populations and show that the fraction of mutants at a given point in space and time obeys a linear response law of the type introduced in this paper. The theory may be used for evaluating the geographic position and the moment in time where and when a mutation originated.
    Physical Review E 07/2002; 65(6 Pt 1):061110. · 2.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The variation of 77 biallelic sites located in the nonrecombining portion of the Y chromosome was examined in 608 male subjects from 22 African populations. This survey revealed a total of 37 binary haplotypes, which were combined with microsatellite polymorphism data to evaluate internal diversities and to estimate coalescence ages of the binary haplotypes. The majority of binary haplotypes showed a nonuniform distribution across the continent. Analysis of molecular variance detected a high level of interpopulation diversity (PhiST=0.342), which appears to be partially related to the geography (PhiCT=0.230). In sub-Saharan Africa, the recent spread of a set of haplotypes partially erased pre-existing diversity, but a high level of population (PhiST=0.332) and geographic (PhiCT=0.179) structuring persists. Correspondence analysis shows that three main clusters of populations can be identified: northern, eastern, and sub-Saharan Africans. Among the latter, the Khoisan, the Pygmies, and the northern Cameroonians are clearly distinct from a tight cluster formed by the Niger-Congo-speaking populations from western, central western, and southern Africa. Phylogeographic analyses suggest that a large component of the present Khoisan gene pool is eastern African in origin and that Asia was the source of a back migration to sub-Saharan Africa. Haplogroup IX Y chromosomes appear to have been involved in such a migration, the traces of which can now be observed mostly in northern Cameroon.
    The American Journal of Human Genetics 06/2002; 70(5):1197-214. · 10.99 Impact Factor
  • Source
    Science 05/2002; 296(5566):261-2. · 31.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The genetic structure of 126 Ethiopian and 139 Senegalese Y chromosomes was investigated by a hierarchical analysis of 30 diagnostic biallelic markers selected from the worldwide Y-chromosome genealogy. The present study reveals that (1) only the Ethiopians share with the Khoisan the deepest human Y-chromosome clades (the African-specific Groups I and II) but with a repertoire of very different haplotypes; (2) most of the Ethiopians and virtually all the Senegalese belong to Group III, whose precursor is believed to be involved in the first migration out of Africa; and (3) the Ethiopian Y chromosomes that fall into Groups VI, VIII, and IX may be explained by back migrations from Asia. The first observation confirms the ancestral affinity between the Ethiopians and the Khoisan, which has previously been suggested by both archaeological and genetic findings.
    The American Journal of Human Genetics 02/2002; 70(1):265-8. · 10.99 Impact Factor
  • Neil Risch, Alberto Piazza, L Luca Cavalli-Sforza
    Nature 02/2002; 415(6868):115. · 42.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: An assessment of 28 pertinent binary genetic markers on the non-recombining portion of the Y chromosome (NRY) in New Zealand Maori and other relevant populations has revealed a diverse genetic paternal heritage of extant Maori. A maximum parsimony phylogeny was constructed in which nine of the 25 possible binary haplotypes were observed. Although ∼40% of the samples have haplotypes of unequivocal European origin, an equivalent number of samples have a single binary haplotype that is also observed in Indonesia and New Guinea, indicative of common indigenous Melanesian ancestry. The balance of the lineages has either typical East Asian signatures or alternative compositions consistent with their affinity to Melanesia or New Guinea. Molecular analysis of mtDNA variation confirms the presence of a single predominant characteristic Southeast Asian (9-bp deletion in the Region V) lineage. The Y-chromosome results support a pattern of complex interrelationships between Southeast Asia, Melanesia, and Polynesia, in contrast to mtDNA and linguistic data, which uphold a rapid and homogeneous Austronesian expansion. The Y-chromosome data highlight a distinctive gender-modulated pattern of differential gene flow in the history of Polynesia. Hum Mutat 17:271–280, 2001. © 2001 Wiley-Liss, Inc.
    Human Mutation 03/2001; 17(4):271 - 280. · 5.05 Impact Factor
  • Source
    Joanna L. Mountain, L. Luca Cavalli-Sforza
    [Show abstract] [Hide abstract]
    ABSTRACT: Our goal is to infer, from human genetic data, general patterns as well as details of human evolutionary history. Here we present the results of an analysis of genetic data at the level of the individual. A tree relating 144 individuals from 12 human groups of Africa, Asia, Europe, and Oceania, inferred from an average of 75 DNA polymorphisms/individual, is remarkable in that most individuals cluster with other members of their regional group. In order to interpret this tree, we consider the factors that influence the tree pattern, including the number of genetic loci examined, the length of population isolation, the sampling process, and the extent of gene flow among groups. Understanding the impact of these factors enables us to infer details of human evolutionary history that might otherwise remain undetected. Our analyses indicate that some recent ancestor(s) of each of a few of the individuals tested may have immigrated. In general, the populations within regional groups appear to have been isolated from one another for <25,000 years. Regional groups may have been isolated for somewhat longer.
    The American Journal of Human Genetics 09/1997; 61(3):705-18. · 10.99 Impact Factor
  • L. Luca Cavalli-Sforza, Alberto Piazza
    Science 01/1995; 267:1530-1532. · 31.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: To determine the human Y-chromosome haplogroup backgrounds of non-consensus DYS458.2 short tandem repeat alleles and evaluate their phylogenetic substructure and frequency in representative samples from the Middle East, Europe, and Pakistan. Methods: Molecular characterization of lineages was achieved using a combination of Y-chromosome haplogroup defining binary polymorphisms and up to 37 short tandem repeat loci, including DYS388 to construct haplotypes. DNA sequencing of the DYS458 locus and median-joining network analyses were used to evaluate Y-chromosome lineages displaying the DYS458.2 motif. Results: We showed that the DYS458.2 allelic innovation arose independently on at least two distinctive binary haplogroup backgrounds and possibly a third as well. The partial allele length pattern was fixed in all haplogroup J1 chromosomes examined, including its known rare sub-haplogroups. Within the alternative R1b3 associated M405 defined sub-haplogroup, both DYS458.0 and DYS458.2 allele classes occurred. A single chromosome also allocated to the R1b3-M269*(xM405) classification. The physical position of the partial insertion/deletion occurrence within the normal tetramer tract differed distinctly in each haplogroup context. Conclusions: While unusual DYS458.2 alleles are informative, additional information for other linked polymorphic loci is required when using such non-conforming alleles to infer haplogroup background and common ancestry.
    Croatian Medical Journal (cmj@mef.hr); Vol.48 No.4.
  • Luigi Luca Cavalli-Sforza
    Kos 25(266):49-60.
  • Source

Publication Stats

3k Citations
352.20 Total Impact Points


  • 2002–2009
    • Stanford Medicine
      • • Department of Genetics
      • • Stanford School of Medicine
      Stanford, California, United States
    • University of Pavia
      • Department of Biology and Biotechnology "Lazzaro Spallanzani"
      Pavia, Lombardy, Italy
    • Sapienza University of Rome
      Roma, Latium, Italy
    • Università della Calabria
      • Department of Cell Biology
      Rende, Calabria, Italy
  • 2001–2009
    • Stanford University
      • • Department of Genetics
      • • Department of Medicine
      Palo Alto, California, United States
  • 2006
    • Indian Statistical Institute
      • Human Genetics Unit (HGU)
      Baranagar, Bengal, India
  • 1997
    • University of California, Berkeley
      • Department of Integrative Biology
      Berkeley, MO, United States