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1.
J Appl Genet ; 60(3-4): 319-328, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31401728

ABSTRACT

This review presents the state-of-the-art in the forensic application of genetic methods driven by the research in population transcriptomics. In the first part of the review, the constraints of using classical genomic markers are shortly reviewed. In the second part, the developments in the field of inter-population diversity at the transcriptomic level are presented. Subsequently, a potential of population-specific transcriptomic markers in forensic science applications, including ascertaining population affiliation of human samples and cell mixtures separation, are presented.


Subject(s)
DNA Fingerprinting , Forensic Sciences/trends , Genetic Variation/genetics , Transcriptome/genetics , Cell Separation/methods , Humans
2.
BMC Genet ; 19(1): 54, 2018 08 07.
Article in English | MEDLINE | ID: mdl-30086702

ABSTRACT

BACKGROUND: Numerous studies have demonstrated significant differences in the expression level across continental human populations. Most of published results were performed on B-cell lines materials examined under specific laboratory conditions, without further validation in a primary biological material. The goal of our study was to identify mRNA markers characterized by a significant and stable difference in the gene expression profile in Caucasian and Chinese populations, both in the commercially available B-lymphocyte cell lines and in the primary samples of the peripheral blood. RESULTS: The preliminary selection of population-differentiating transcripts was based on Illumina expression microarray analysis of the representative group of ethnically-specified B-lymphocyte cell lines. Twenty genes with the inter-population difference in the mean expression characterized by the at least 1.5-fold change and FDR <  0.05 were identified. Subsequently, a two-step validation procedure was carried out. In the first step, a subset of selected population- differentiating transcripts was tested in the independent set of B-lymphocyte cell lines, using TLDA cards. Based on TLDA analysis, three transcripts representing Fch > 2 were chosen for validation. The differentiating status was confirmed for all of them: UTS2, UGT2B17 and SLC7A7. The mean expression of UTS2 was higher in CHB (25.8-fold change compared to CEU), while the expression of UGT2B17 and SLC7A7 was higher in CEU (3.2- and 2.2-fold change, respectively). In the next validation step, two transcripts were verified in the primary biological material. As an ultimate result of our study, two mRNA markers (UTS2 and UGT2B17) exhibiting population differences in the expression level in both B-cell line and in the blood were identified. Further statistical analysis confirmed the discriminatory potential of these two markers. CONCLUSIONS: An inter-population differences on the level of gene expression were identified in both B-cell lines and peripheral blood samples. These findings may have a practical application in the field of forensic science. In particular, these transcripts, targeted by specific probes, may be used as population-specific targets in the efforts aiming to separate mixture of blood from individuals of different populations. Notwithstanding, these results have to be confirmed on extended population group.


Subject(s)
Molecular Typing/methods , Transcriptome , Asian People/genetics , Biomarkers , Cell Line , Forensic Genetics/methods , Gene Expression Profiling , Humans , Male , Real-Time Polymerase Chain Reaction , Sequence Analysis, RNA , White People/genetics
3.
Forensic Sci Int Genet ; 20: 89-100, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26520215

ABSTRACT

Assays that allow analysis of the biogeographic origin of biological samples in a standard forensic laboratory have to target a small number of highly differentiating markers. Such markers should be easy to multiplex and the assay must perform well in the degraded and scarce biological material. SNPs localized in the genome regions, which in the past were subjected to differential selective pressure in various populations, are the most widely used markers in the studies of biogeographic affiliation. SNPs reflecting biogeographic differences not related to any phenotypic traits are not sufficiently explored. The goal of our study was to identify a small set of SNPs not related to any known pigmentation/phenotype-specific genes, which would allow efficient discrimination between populations of Europe and East Asia. The selection of SNPs was based on the comparative analysis of representative European and Chinese/Japanese samples (B-lymphocyte cell lines), genotyped using the Infinium HumanOmniExpressExome microarray (Illumina). The classifier, consisting of 24 unlinked SNPs (24-SNP classifier), was selected. The performance of a 14-SNP subset of this classifier (14-SNP subclassifier) was tested using genotype data from several populations. The 14-SNP subclassifier differentiated East Asians, Europeans and Africans with ∼100% accuracy; Palestinians, representative of the Middle East, clustered with Europeans, while Amerindians and Pakistani were placed between East Asian and European populations. Based on these results, we have developed a SNaPshot assay (EurEAs_Gplex) for genotyping SNPs from the 14-SNP subclassifier, combined with an additional marker for gender identification. Forensic utility of the EurEAs_Gplex was verified using degraded and low quantity DNA samples. The performance of the EurEAs_Gplex was satisfactory when using degraded DNA; tests using low quantity DNA samples revealed a previously not described source of genotyping errors, potentially important for any SNaPshot-based assays.


Subject(s)
Asian People/genetics , Forensic Genetics/methods , Racial Groups/genetics , White People/genetics , DNA/analysis , DNA/blood , DNA/genetics , DNA Primers , Gene Frequency , Genetics, Population , Genotype , Humans , Male , Multiplex Polymerase Chain Reaction/methods , Phenotype , Phylogeography , Polymorphism, Single Nucleotide , Racial Groups/classification , Sex Determination Analysis/methods
4.
J Appl Genet ; 50(3): 261-73, 2009.
Article in English | MEDLINE | ID: mdl-19638683

ABSTRACT

Analysis of relationships between the ageing cell phenotype and the age of cell donors is one of the ways towards understanding the link between cellular and organismal ageing. Cytogenetically, ageing is associated with a number of gross cellular changes, including altered size and morphology, genomic instability, and changes in expression and proliferation. Genomic instability can be easily assessed by analyzing the level of cytogenetic aberrations. In this review, we focus on the differences in the level and profile of cytogenetic aberrations observed in donors of different age and gender. Centenarians are a small fraction of the population at the extreme of human longevity. Their inclusion in such studies may shed light on one of the basic questions: whether genome stability is better maintained in successfully aged individuals compared to the rest of the population. At the same time, comparing the profile of age-related amount of chromosomal aberrations in men and women may help explaining the commonly observed gender differences in longevity.


Subject(s)
Aging/genetics , Chromosome Aberrations , Longevity/genetics , Female , Genomic Instability/genetics , Humans , Male , Polyploidy , Sex Factors
5.
J Med Genet ; 43(1): e1, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16397065

ABSTRACT

BACKGROUND: Primary ciliary dyskinesia (PCD) is a genetic disorder caused by ciliary immotility/dysmotility due to ultrastructural defects of the cilia. Kartagener syndrome (KS), a subtype of PCD, is characterised by situs inversus accompanying the typical PCD symptoms of bronchiectasis and chronic sinusitis. In most cases, PCD is transmitted as an autosomal recessive trait, but its genetic basis is unclear due to extensive genetic heterogeneity. METHODS: In a genome-wide search for PCD loci performed in 52 KS families and in 18 PCD families with no situs inversus present (CDO, ciliary dysfunction-only), the maximal pairwise LOD score of 3.36 with D15S205 in the KS families indicated linkage of a KS locus to the long arm of chromosome 15. In the follow-up study, 65 additional microsatellite markers encompassing D15S205 were analysed. RESULTS: A maximal pairwise LOD score of 4.34 was observed with D15S154, further supporting linkage of the KS, but not the CDO, families to 15q24-25. Analysis of heterogeneity and haplotypes suggested linkage to this region in 60% of KS families. CONCLUSIONS: Reinforced by the results of multipoint linkage, our analyses indicate that a major KS locus is localised within a 3.5 cM region on 15q, between D15S973 and D15S1037.


Subject(s)
Chromosome Mapping , Chromosomes, Human, Pair 15/genetics , Kartagener Syndrome/genetics , Lod Score , Chromosome Segregation , Gene Frequency , Haplotypes , Humans , Microsatellite Repeats/genetics
6.
Am J Hum Genet ; 69(5): 1113-26, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11582570

ABSTRACT

We studied mutations in the mtDNA control region (CR) using deep-rooting French-Canadian pedigrees. In 508 maternal transmissions, we observed four substitutions (0.0079 per generation per 673 bp, 95% CI 0.0023-0.186). Combined with other familial studies, our results add up to 18 substitutions in 1,729 transmissions (0.0104), confirming earlier findings of much greater mutation rates in families than those based on phylogenetic comparisons. Only 12 of these mutations occurred at independent sites, whereas three positions mutated twice each, suggesting that pedigree studies preferentially reveal a fraction of highly mutable sites. Fitting the data through use of a nonuniform rate model predicts the presence of 40 (95% CI 27-54) such fast sites in the whole CR, characterized by the mutation rate of 274 per site per million generations (95% CI 138-410). The corresponding values for hypervariable regions I (HVI; 1,729 transmissions) and II (HVII; 1,956 transmissions), are 19 and 22 fast sites, with rates of 224 and 274, respectively. Because of the high probability of recurrent mutations, such sites are expected to be of no or little informativity for the evaluation of mutational distances at the phylogenetic time scale. The analysis of substitution density in the alignment of 973 HVI and 650 HVII unrelated European sequences reveals that the bulk of the sites mutate at relatively moderate and slow rates. Assuming a star-like phylogeny and an average time depth of 250 generations, we estimate the rates for HVI and HVII at 23 and 24 for the moderate sites and 1.3 and 1.0 for the slow sites. The fast, moderate, and slow sites, at the ratio of 1:2:13, respectively, describe the mutation-rate heterogeneity in the CR. Our results reconcile the controversial rate estimates in the phylogenetic and familial studies; the fast sites prevail in the latter, whereas the slow and moderate sites dominate the phylogenetic-rate estimations.


Subject(s)
DNA, Mitochondrial/genetics , Mutation/genetics , Phylogeny , Regulatory Sequences, Nucleic Acid/genetics , Canada , Europe , Female , France/ethnology , Humans , Kinetics , Male , Models, Genetic , Mutagenesis/genetics , Pedigree , Sequence Alignment
7.
J Appl Genet ; 42(4): 509-30, 2001.
Article in English | MEDLINE | ID: mdl-14564026

ABSTRACT

Dynamic advance in DNA sequencing methods and progress in formal population genetics analyses made it possible to infer aspects of human evolution from the DNA diversity distribution and frequency in contemporary populations. While providing some general background concerning the origins of modern human, this paper focuses on the dynamics of prehistoric population in Europe. The relevance of the present-day genetic diversity studies in elucidating prehistoric events is presented in the context of archeological and paleoanthropological evidence. The questions of the Neanderthal admixture as well as of the relative contribution of different waves of prehistoric migrations to the gene pool of modern Europeans are discussed.

8.
Genetics ; 156(2): 799-808, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11014825

ABSTRACT

An important question in the ongoing debate on the origin of Homo sapiens is whether modern human populations issued from a single lineage or whether several, independently evolving lineages contributed to their genetic makeup. We analyzed haplotypes composed of 35 polymorphisms from a segment of the dystrophin gene. We find that the bulk of a worldwide sample of 868 chromosomes represents haplotypes shared by different continental groups. The remaining chromosomes carry haplotypes specific for the continents or for local populations. The haplotypes specific for non-Africans can be derived from the most frequent ones through simple recombination or a mutation. In contrast, chromosomes specific for sub-Saharan Africans represent a distinct group, as shown by principal component analysis, maximum likelihood tree, structural comparison, and summary statistics. We propose that African chromosomes descend from at least two lineages that have been evolving separately for a period of time. One of them underwent range expansion colonizing different continents, including Africa, where it mixed with another, local lineage represented today by a large fraction of African-specific haplotypes. Genetic admixture involving archaic lineages appears therefore to have occurred within Africa rather than outside this continent, explaining greater diversity of sub-Saharan populations observed in a variety of genetic systems.


Subject(s)
Black People/genetics , Chromosome Mapping , Hominidae/genetics , Phylogeny , White People/genetics , Africa , Africa South of the Sahara , Algorithms , Animals , Databases as Topic , Female , Haplotypes , Humans , Likelihood Functions , Male , X Chromosome , Y Chromosome
9.
Mol Biol Evol ; 16(11): 1633-40, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10555294

ABSTRACT

DNA variability was investigated in the last intron of the Y-chromosome-specific zinc finger gene, ZFY, and its X homolog on Xp21.3, ZFX. No polymorphisms were found in the 676-bp ZFY segment in a sample of 205 world-wide-distributed Y chromosomes, other than a solitary nucleotide variant in one individual (nucleotide diversity pi = 0.0014%). In contrast, 10 segregating sites (pi = 0.082%) were identified within 1,089 bp of the ZFX sequence in a sample of 336 X chromosomes. Four of these polymorphisms, which contributed most of the diversity, were located within an Alu insert disrupting the ZFY-ZFX homology (pi Alu = 0.24%). The diversity in the homologous portion of the ZFX intron, although higher than that in ZFY, was lower than that found in genomic segments believed to evolve neutrally; interspecies divergence in both segments was also reduced. Although this suggests that the evolution of both ZFY and ZFX homologs may not be entirely neutral, both Tajima and HKA tests did not reject neutrality. The lack of statistical significance may be attributed to a lack of power in these tests (the low divergence and variability values reduce the power of the HKA and Tajima tests, respectively); furthermore, Homo sapiens has recently undergone a rapid population growth, and selection is more difficult to detect in an expanding population. Therefore, the failure to reject neutrality does not necessarily indicate the absence of selection. In this context, the phylogenetic argument was given more weight in out interpretations. The high level of sequence identity in ZFY and ZFX segments, in spite of their separation 80-130 MYA, reflects a lower mutation rate as compared with other segments believed to undergo unconstrained evolution. Thus, the possibility of weak selection contributing to the low level of nucleotide diversity in the last ZFY intron cannot be excluded and should be kept in mind in the population genetics studies based on Y chromosome variability.


Subject(s)
DNA-Binding Proteins/genetics , Genetic Variation , Introns , Selection, Genetic , Base Sequence , DNA Primers , Evolution, Molecular , Humans , Kruppel-Like Transcription Factors , Polymorphism, Single Nucleotide , Transcription Factors , Zinc Fingers
10.
Genetics ; 152(3): 1091-101, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10388827

ABSTRACT

With 10 segregating sites (simple nucleotide polymorphisms) in the last intron (1089 bp) of the ZFX gene we have observed 11 haplotypes in 336 chromosomes representing a worldwide array of 15 human populations. Two haplotypes representing 77% of all chromosomes were distributed almost evenly among four continents. Five of the remaining haplotypes were detected in Africa and 4 others were restricted to Eurasia and the Americas. Using the information about the ancestral state of the segregating positions (inferred from human-great ape comparisons), we applied coalescent analysis to estimate the age of the polymorphisms and the resulting haplotypes. The oldest haplotype, with the ancestral alleles at all the sites, was observed at low frequency only in two groups of African origin. Its estimated age of 740 to 1100 kyr corresponded to the time to the most recent common ancestor. The two most frequent worldwide distributed haplotypes were estimated at 550 to 840 and 260 to 400 kyr, respectively, while the age of the continentally restricted polymorphisms was 120 to 180 kyr and smaller. Comparison of spatial and temporal distribution of the ZFX haplotypes suggests that modern humans diverged from the common ancestral stock in the Middle Paleolithic era. Subsequent range expansion prevented substantial gene flow among continents, separating African groups from populations that colonized Eurasia and the New World.


Subject(s)
DNA-Binding Proteins/genetics , Genealogy and Heraldry , Haplotypes , Introns , Polymorphism, Genetic , Humans , Kruppel-Like Transcription Factors , Male , Models, Genetic , Time Factors , Transcription Factors , X Chromosome
11.
Mol Phylogenet Evol ; 11(1): 77-83, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10082612

ABSTRACT

Related genomes tend to be colonized by the same or similar repetitive sequence elements. Analysis of these elements provides useful taxonomic information. We have sequenced Alu repeats from tarsier and compared them with those from strepsirhine prosimians (lemurs, sifaka, and galago) and the human genome. Tarsier elements cluster with Alu subfamilies from the human lineage. The oldest subfamily in tarsier and the most abundant human subfamilies share an RNA secondary structure motif which is absent both in the earliest dimeric Alu Jo and in the strepsirhine elements. These findings are consistent with the view that tarsiers form a sister clade with anthropoides rather than with other prosimians. Alu repeats in tarsier genome are relatively old, which indicates a dramatic slowdown or even an arrest of these elements' amplification about 20 Myr ago.


Subject(s)
Alu Elements/genetics , Phylogeny , Primates/genetics , Tarsiidae/genetics , Animals , Base Sequence , DNA Transposable Elements/genetics , Evolution, Molecular , Humans , Molecular Sequence Data , Nucleic Acid Conformation , RNA/chemistry , RNA/genetics , Sequence Homology, Nucleic Acid
12.
J Mol Evol ; 47(2): 146-55, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9694663

ABSTRACT

Neutral DNA polymorphisms from an 8-kb segment of the dystrophin gene, previously ascertained in a worldwide sample (n = 250 chromosomes), were used to characterize the population ancestral to the present-day human groups. The ancestral state of each polymorphic site was determined by comparing human variants with their orthologous sites in the great apes. The "age before fixation" of the underlying mutations was estimated from the frequencies of the new alleles and analyzed in the context of these polymorphisms' distribution among 13 populations from Africa, Europe, Asia, New Guinea, and the Americas (n = 860 chromosomes in total). Seventeen polymorphisms older tan 100,000-200,000 years, which contributed approximately 90% to the overall nucleotide diversity, were common to all human groups. Polymorphisms endemic to human groups or continentally restricted were younger than 100,000-200,000 years. Africans (six populations) with 13 such sites stood out from the rest of the world (seven populations), where only 2 population-specific variants were observed. The similarity of the frequencies of the old polymorphisms in Africans and non-Africans suggested a similar profile of genetic variability in the population before the modern human's divergence. This ancestral population was characterized by an effective size of about 10,000 as estimated from the nucleotide diversity; this size may describe the number of breeding individuals over a long time during the Middle Pleistocene or reflect a speciation bottleneck from an initially larger population at the end of this period.


Subject(s)
Dystrophin/genetics , Evolution, Molecular , Hominidae/genetics , Racial Groups/genetics , Alleles , Animals , Gene Frequency , Humans , Models, Genetic , Mutagenesis , Mutation , Polymorphism, Genetic , Time
13.
J Mol Evol ; 47(2): 172-82, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9694666

ABSTRACT

To get insight into the early evolution of the primate Alu elements, we characterized sequences of these repeats from the Malagasy prosimians, lemurs (Lemuridae) and sifakas (Indriidae), as well as from galagos (Lorisidae). These sequences were compared with the oldest Alu species known from the human genome: dimeric Alu J and S and free Alu monomers. Our analysis indicates that about 60 Myr ago, before the prosimian divergence, free left and right monomers formed an Alu heterodimer connected by a 19-nucleotide-long A-rich linker. The resulting elements successfully propagated in diverging primate lineages until about approximately 20 Myr ago, conserving similar sequence features and essentially the same Alu RNA secondary structure. We suggest that until that time the same "retropositional niche", molecular machinery making possible the proliferation by retroposition, constrained the evolution of Alu elements in extant primate species. These constraints became subsequently relaxed. In the Malagasy prosimians the dimeric Alu continued to amplify after acquiring a 34- to 36-nucleotide extension of their linker segment, whereas in the galago genome the "retropositional niche" was occupied by novel short elements.


Subject(s)
Evolution, Molecular , RNA/genetics , Repetitive Sequences, Nucleic Acid , Strepsirhini/genetics , Animals , Base Sequence , Consensus Sequence , Humans , Likelihood Functions , Madagascar , Molecular Sequence Data , Nucleic Acid Conformation , RNA/chemistry , RNA, Small Cytoplasmic , Sequence Homology, Nucleic Acid , Strepsirhini/classification
15.
Gene ; 205(1-2): 161-71, 1997 Dec 31.
Article in English | MEDLINE | ID: mdl-9461390

ABSTRACT

Nucleotide variation was examined in an 8 kb intronic DNA bordering exon 44 of the human dystrophin gene on Xp21. Thirty-six polymorphisms (substitutions, small insertions/deletions and one (T)n microsatellite) were found using SSCP/heteroduplex analysis of DNA samples from mixed Europeans, Papua New Guineans as well as from six African, three Asian and two Amerindian populations. In this way the European bias in the nuclear polymorphism ascertainment has been avoided. In a maximum likelihood tree constructed from the frequency data, Africans clustered separately from the non-African populations. Fifteen polymorphisms were shared among most of the populations compared, whereas 13 sites were found to be endemic to Africans and four to non-Africans. The common sites contributed most to the average heterozygosity (Hn=0.101%+/-0.023), whereas the endemic ones, being rare, had little effect on this estimate. The F(ST) values were lower for Africans (0.072) than for non-Africans (0.158), suggesting a higher level of gene exchange within Africa, corroborating the observation of a greater number of segregating sites on this continent than elsewhere. The data suggest a recent common origin of the African and non-African populations, where a greater geographical isolation of the latter resulted in a smaller number of newly acquired polymorphisms.


Subject(s)
Cell Nucleus/metabolism , DNA/genetics , Genetic Variation , Gene Frequency , Humans , Polymorphism, Single-Stranded Conformational , Species Specificity , X Chromosome
17.
Science ; 274(5287): 631a, 1996 Oct 25.
Article in English | MEDLINE | ID: mdl-17759701
18.
Genomics ; 36(3): 388-98, 1996 Sep 15.
Article in English | MEDLINE | ID: mdl-8884261

ABSTRACT

We studied two systems of multilocus markers revealed by PCR using primers directing amplification between Alu repeats in a tail-to-tail orientation. Genomic polymorphisms were detected as the presence or absence of the electrophoretic bands representing DNA fragments of a given length. A total of 104 such fragments segregating as Mendelian markers in a panel of eight CEPH families were analyzed by two-point linkage analysis. Fifty-one of these fragments were localized with respect to CEPH markers; they represented 33 loci, 7 of which were multiallelic. Locus-specific oligonucleotides were developed and used as hybridization probes to identify the mapped loci within a complex pattern of inter-Alu PCR products. A great proportion of inter-Alu PCR polymorphisms represented length variants within amplified DNA segments, while others were presumably due to mutations within the priming sites. To describe the expected number of informative loci per typing experiment we introduced a parameter called overall informativity (OI), which provides a single measure of the multiplex ratio and the informativity of markers contributing to a multilocus system (OI of a single locus is equivalent to its heterozygosity and cannot exceed 0.5 for a biallelic codominant marker). High OI values (5.8 and 11.5) of the two presented systems of inter-Alu PCR markers of random chromosomal distribution render them suitable for mapping genomic rearrangements such as genomic deletions in tumoral tissues. This was illustrated by the detection of loss of heterozygosity in the 9q22-qter region in sporadic colon cancer.


Subject(s)
Gene Rearrangement , Polymorphism, Genetic , Repetitive Sequences, Nucleic Acid , Animals , Chromosome Mapping , Cloning, Molecular , Cricetinae , Genetic Linkage , Genetic Markers , Humans , Hybrid Cells , Polymerase Chain Reaction
19.
Am J Hum Genet ; 59(3): 633-43, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8751865

ABSTRACT

Pseudo-vitamin D-deficiency rickets (PDDR) was mapped close to D12S90 and between proximal D12S312 and distal (D12S305, D12S104) microsatellites that were subsequently found on a single YAC clone. Analysis of a complex haplotype in linkage disequilibrium (LD) with the disease discriminated among distinct founder effects in French Canadian populations in Acadia and in Charlevoix-Saguenay-Lac-Saint-Jean (Ch-SLSJ), as well as an earlier one in precolonial Europe. A simple demographic model suggested the historical age of the founder effect in Ch-SLSJ to be approximately 12 generations. The corresponding LD data are consistent with this figure when they are analyzed within the framework of Luria-Delbrück model, which takes into account the population growth. Population sampling due to a limited number of first settlers and the rapid demographic expansion appear to have played a major role in the founding of PDDR in Ch-SLSJ and, presumably, other genetic disorders endemic to French Canada. Similarly, the founder effect in Ashkenazim, coinciding with their early settlement in medieval Poland and subsequent expansion eastward, could explain the origin of frequent genetic diseases in this population.


Subject(s)
Founder Effect , Linkage Disequilibrium , Rickets/genetics , Vitamin D Deficiency/genetics , Base Sequence , Canada/epidemiology , Chromosome Mapping , Chromosomes, Human, Pair 12/genetics , Demography , Female , France/ethnology , Haplotypes , Humans , Male , Molecular Sequence Data , Rickets/ethnology , Vitamin D Deficiency/ethnology
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