Alu insertion polymorphisms (polymorphisms consisting of the presence/absence of an Alu element at a particular chromosomal location) offer several advantages over other nuclear DNA polymorphisms for human evolution studies. First, they are typed by rapid, simple, PCR-based assays; second, they are stable polymorphisms-newly inserted Alu elements rarely undergo deletion; third, the presence of an Alu element represents identity by descent-the probability that different Alu elements would independently insert into the exact same chromosomal location is negligible; and fourth, the ancestral state is known with certainty to be the absence of an Alu element. We report here a study of 8 loci in 1500 individuals from 34 worldwide populations. African populations exhibit the most between-population differentiation, and the population tree is rooted in Africa; moreover, the estimated effective time of separation of African versus non-African populations is 137,000 ± 15,000 years ago, in accordance with other genetic data. However, a principal coordinates analysis indicates that populations from Sahul (Australia and New Guinea) are nearly as close to the hypothetical ancestor as are African populations, suggesting that there was an early expansion of tropical populations of our species. An analysis of heterozygosity versus genetic distance suggests that African populations have had a larger effective population size than non-African populations. Overall, these results support the African origin of modern humans in that an earlier expansion of the ancestors of African populations is indicated.The Alu family of short interspersed elements is one of the most successful mobile genetic elements, having arisen to a copy number in excess of 500,000 within primate genomes in the last 65 million years (for recent reviews, see Okada 1991;Schmid and Maraia 1992; Batzer 1993, 1995). Alu repeats are thought to be ancestrally derived from the 7SL RNA gene and mobilize through an RNA polymerase III-derived transcript in a process termed retroposition. Each Alu sequence is ∼300bp in length; therefore, Alu repeats comprise ∼5% of the human genome.Alu sequences can be divided into different subfamilies or clades of related elements based on commonly shared diagnostic mutations. Here, we use the new standardized nomenclature to refer to various Alu subfamilies (Batzer et al. 1996a). Two of the most recently formed subfamilies of Alu elements within the human genome have been termed Ya5 and Ya8 (Batzer et al. 1990;. Members of the Ya8 Alu subfamily are characterized by all five of the Ya5 diagnostic mutations, as well as three additional diagnostic mutations. Be- GENOME RESEARCH 1061Cold Spring Harbor Laboratory Press on May 12, 2018 -Published by genome.cshlp.org Downloaded from cause both the Ya5 and Ya8 Alu subfamilies share a number of diagnostic mutations we refer to this lineage collectively as Ya5/8 (Batzer et al. 1996b). The Ya5/8 Alu subfamily lineage is comprised of 500-2000 elements that are restricted to the human genome (Arco...

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The Alu family of interspersed repeats is comprised of over 500,000 members which may be divided into discrete subfamilies based upon mutations held in common between members. Distinct subfamilies of Alu sequences have amplified within the human genome in recent evolutionary history. Several individual Alu family members have amplified so recently in human evolution that they are variable as to presence and absence at specific loci within different human populations. Here, we report on the distribution of six polymorphic Alu insertions in a survey of 563 individuals from 14 human population groups across several continents. Our results indicate that these polymorphic Alu insertions probably have an African origin and that there is a much smaller amount of genetic variation between European populations than that found between other population groups.

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The chromosomal translocation t(11;14)(q13;q32) fuses the IGH and CCND1 genes and leads to cyclin D1 overexpression. This genetic abnormality is the hallmark of mantle cell lymphoma (MCL), but is also found in some cases of atypical chronic lymphocytic leukemia (CLL), characterized by a poor outcome. For an unequivocal assessment of this specific chromosomal rearrangement on interphase cells, we developed a set of probes for fluorescence in situ hybridization (FISH). Northern blotting was performed for analysis of the cyclin D1 expression in 18 patients. Thirty-eight patients, with either a typical MCL leukemic phase (17 patients) or atypical CLL with an MCL-type immunophenotype, i.e., CD19 ϩ , CD5 ϩ , CD23 -/low , CD79b/ sIgM(D) ϩϩ , and FMC7 ϩ (21 patients), were analyzed by dual-color interphase FISH. We selected an IGH-specific BAC probe (covering the JH and first constant regions) and a commercially available CCND1 probe. An IGH-CCND1 fusion was detected in 28 of the 38 patients (17 typical MCL and 11 cases with CLL). Cyclin D1 was not overexpressed in two patients with typical MCL and an IGH-CCND1 fusion. In view of the poor prognosis associated with MCL and t(11;14)-positive CLL, we conclude that this set of probes is a valuable and reliable tool for a rapid diagnosis of these entities.