Biomedical subjects

D Labuda

Publications and source records attributed to D Labuda.

At least 19 recordsLinked to original sources

PubMed2006

Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity.

N-acetyltransferase 2 (NAT2), an important enzyme in clinical pharmacology, metabolizes antibiotics such as isoniazid and sulfamethoxazole, and catalyzes the transformation of aromatic and heterocyclic amines from the environment and diet into carcinogenic intermediates. Polymorphisms in NAT2 account for variability in the acetylator phenotype and the pharmacokinetics of metabolized drugs. Native Americans, settled in rural areas and large cities of Latin America, are under-represented in pharmacogenetics studies; therefore, we sequenced the coding region of NAT2 in 456 chromosomes from 13 populations from the Americas, and two from Siberia, detecting nine substitutions and 11 haplotypes. Variants *4 (37%), *5B (23%) and *7B (24%) showed high frequencies. Average frequencies of fast, intermediate and slow acetylators across Native Americans were 18, 56 and 25%, respectively. NAT2 intra-population genetic diversity for Native Americans is higher than East Asians and similar to the rest of the world, and NAT2 variants are homogeneously distributed across native populations of the continent.

Acetylation↗

PubMed2005

Ethiopia: between Sub-Saharan Africa and western Eurasia.

Ethiopia is central to population genetic studies investigating the out of Africa expansion of modern humans, as shown by Y chromosome and mtDNA studies. To address the level of genetic differentiation within Ethiopia, and its relationship to Sub-Saharan Africa and Eurasia, we studied an 8 kb segment of the X-chromosome from 72 chromosomes from the Amhara, Oromo and Ethiopian Jews, and compared these results with 804 chromosomes from Middle Eastern, African, Asian and European populations, and 22 newly typed Saharawi. Within Ethiopia the two largest ethnic groups, the Amhara and Oromo, were not found to be statistically distinct, based on an exact test of haplotype frequencies. The Ethiopian Jews appear as an admixed population, possibly of Jewish origin, though the data remain equivocal. There is evidence of a close relationship between Ethiopian and Yemenite Jews, likely a result of indirect gene flow. Within an African and Eurasian context, the distribution of alleles of a variable T(n) repeat, and the spread of haplotypes containing Africa-specific alleles, provide evidence of a genetic continuity from Sub-Saharan Africa to the Near East, and furthermore suggest that a bottleneck occurred in Ethiopia associated with an out of Africa expansion. Ethiopian genetic heterogeneity, as evidenced by principal component analysis of haplotype frequencies, most likely resulted from periods of subsequent admixture. While these results are from the analysis of one locus, we feel that in association with data from other marker systems they add a complementary perspective on the history of Ethiopia.

Africa↗

PubMed2003

Prostate cancer susceptibility genes: lessons learned and challenges posed.

In most developed countries, prostate cancer is the most frequently diagnosed malignancy in men. The extent to which the marked racial/ethnic difference in its incidence rate is attributable to screening methods, environmental, hormonal and/or genetic factors remains unknown. A positive family history is among the strongest epidemiological risk factors for prostate cancer. It is now well recognized that the role of candidate genetic markers to this multifactorial malignancy is more difficult to identify than the identification of other cancer susceptibility genes. Indeed, despite the localization of several susceptibility loci, there has been limited success in identifying high-risk susceptibility genes analogous to BRCA1 or BRCA2 for breast and ovarian cancer. Nonetheless, three strong candidate susceptibility genes have been described, namely ELAC2 (chromosome 17p11/HPC2 region), 2'-5'-oligoadenylate-dependent ribonuclease L (RNASEL), a gene in the HPC1 region, and Macrophage Scavenger Receptor 1 (MSR1), a gene within a region of linkage on chromosome 8p. Additional studies using larger cohorts are needed to fully evaluate the role of these susceptibility genes in prostate cancer risk. It is also of interest to mention that a significant percentage of men with early-onset prostate cancer harbor germline mutation in the BRCA2 gene thus confirming its role as a high-risk prostate cancer susceptibility gene. Although initial segregation analyses supported the hypothesis that a number of rare highly penetrant loci contribute to the Mendelian inheritance of prostate cancer, current experimental evidence better supports the hypothesis that some of the familial risks may be due to inheritance of multiple moderate-risk genetic variants. In this regard, it is not surprising that analyses of genes encoding key proteins involved in androgen biosynthesis and action led to the observation of a significant association between a susceptibility to prostate cancer and common genetic variants in some of those genes.

Chromosome Mapping↗

PubMed2001

Phylogenetic and familial estimates of mitochondrial substitution rates: study of control region mutations in deep-rooting pedigrees.

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.

Canada↗

PubMed2001

Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen-metabolizing enzymes and gene-environment interactions.

Breast cancer is the most frequent malignancy among women. Since genetic factors such as BRCA1 and BRCA2 as well as reproductive history constitute only 30% of the cause, environmental exposure may play a significant role in the development of breast cancer. Likewise, the relevant enzymes involved in the biotransformation of xenobiotics (from tobacco smoke, diet or other environmental sources) might play a role in breast carcinogenesis. Since individuals with modified ability to metabolize these carcinogens could have a different risk for breast cancer, we investigated the role of cytochromes P-450 (CYP1A1, CYP2D6), glutathione-S-transferases (GSTM1, GSTT1, GSTP1) and N-acetyltransferases (NAT1, NAT2) gene variants in breast carcinogenesis. A case-control study was conducted on 149 women with breast carcinoma and 207 healthy controls, both of French-Canadian origin. The CYP1A1*4 allele was found to be a significant risk determinant of breast carcinoma (OR = 3.3, 95% CI 1.1-9.7), particularly among post-menopausal women (OR = 4.0, 95% CI 1.2-13.8). The frequency of NAT2 rapid acetylators was increased among smokers (OR = 2.6, 95% CI 0.8-8.2), while the NAT1*10 allele conferred a 4-fold increase in risk among women who consumed well-done meat (OR = 4.4, 95% CI 1.0-18.9). These data suggest that CYP1A1*4, NAT1 and NAT2 variants are involved in the susceptibility to breast carcinoma by modifying the impact of exogenous and/or endogenous exposures.

Arylamine N-Acetyltransferase↗

PubMed2000

Unique origin and specific ethnic distribution of the Friedreich ataxia GAA expansion.

The GAA triplet repeat expansion that causes Friedreich ataxia is found only in individuals of European, North African, Middle Eastern, or Indian origin (Indo-European and Afro-Asiatic speakers). Analysis of normal alleles of the GAA repeat and of closely linked markers suggests that expansions arose through a unique two-step process. A major implication of these findings is that Friedreich ataxia may not exist among sub-Saharan Africans, Amerindians, and people from China, Japan, and Southeast Asia.

Africa, Northern↗

PubMed2000

Evolutionary inventions and continuity of CORE-SINEs in mammals.

We characterized short interspersed elements (SINEs), of the CORE-suprafamily in egg-laying (monotremes), pouched (marsupials) and placental mammals. Five families of these repeats distinguished by the presence of distinct LINE-related 3'-segments shared tRNA-like promoter and the central core region. The putative active elements were reconstructed from the alignment of genomic repeats representing molecular fossils of sequences that amplified in the past and since then underwent multiple mutations. Their mode of proliferation by retroposition was indicated by the presence of: (1) internal RNA PolIII promoter; (2) simple sequence repeated tail; (3) direct repeats; and (4) subfamilies recording the evolution of elements. The copy number of CORE-SINEs in placental genomes was estimated at about 300,000; they were highly divergent and apparently ceased to amplify before radiation of these lineages. On the other hand, among almost half a million fossil elements present in marsupials and monotremes, the youngest subfamilies could still be retropositionally active. CORE-SINEs terminate in sequence repeats of a few nucleotides similar to their 3'-segment LINE-homologues, CR1, L2 and Bov-B. These three LINE elements fall into clades distinct from that of L1 elements which, similar to their co-amplifying SINEs, end in a poly(A) tail. We propose a model in which new CORE-families, with distinct 3'-segments, are created at the RNA level due to template switching between LINE and CORE-RNA during reverse transcription. The proposed mechanism suggests that such an adaptation to the changing amplification machinery facilitated the survival and prosperity of CORE-elements over long evolutionary periods in different lineages.

Animals↗

PubMed2000

Parental smoking, CYP1A1 genetic polymorphisms and childhood leukemia (Québec, Canada).

OBJECTIVE: To evaluate the effect of parental smoking on childhood acute lymphoblastic leukemia and to determine if it is modified by child genetic polymorphisms. METHODS: We carried out a case-control study in Quebec, Canada, including 491 incident cases aged 0-9 years and as many healthy controls matched on age and sex. Each parent was interviewed separately with respect to smoking habits during and after pregnancy. In addition, we carried out a case-only substudy with 158 cases classified according to presence or absence of the alleles *2A, *2B, and *4 in the CYP1A1 gene. RESULTS: There were small risk increases with maternal smoking during the later trimesters. Interaction odds ratios were increased (although often not significantly) for the CYP1A1*4 allele at high levels of maternal smoking in the last trimesters and at low level of paternal postnatal smoking, and decreased for the CYP1A1*2B allele. The latter appeared to confer a protective advantage at low levels for maternal prenatal smoking and at high levels for paternal postnatal smoking. CONCLUSIONS: Reported smoking habits showed no association with leukemia; risks for genetic polymorphisms lacked precision but indicated that the effect of parental smoking could be modified by variant alleles in the CYP1A1 gene.

Alleles↗

PubMed2000

Archaic lineages in the history of modern humans.

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.

Africa↗

PubMed2000

Genetic susceptibility to childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. The origin of this disease can be explained by a combination of genetic susceptibility factors and environmental exposures. For the purpose of our study it can be considered as a complex disease, caused by the "carcinogenic" effect of the environment modified by a series of genes. In population, these genes tend to occur in allelic forms representing functional polymorphisms thus explaining inter-individual variability in cancer susceptibility. The latter can be evaluated more realistically in childhood ALL than in sporadic cancers of the adult because of its relatively short latency period. We asked therefore, the question about the role of genes controlling the efficiency of xenobiotics metabolism in childhood leukemogenesis. Xenobiotics (drugs and carcinogens) are excreted from the body after metabolic conversion by enzymes mediating oxidation activation (Phase I) and conjugation detoxificaton (Phase II). Functional variants of these enzymes, resulting from known DNA polymorphisms in the corresponding genes, were shown to influence the risk to a variety of solid tumours in adults. A case-control study on ALL patients and healthy controls in a French-Canadian population was carried out by examining the loci of Phase I, CYP1A1 and CYP2D6, as well as Phase II enzymes, GSTM1, GSTT1, NAT1 and NAT2. The NAT2 slow-acetylator, CYP1A1*2A and GSTM1 null genotypes were shown to be significant risk determinants of ALL (OR=1.6, 1.8 and 1.8, respectively), whereas, polymorphisms in CYP2D6 and GSTT1 genes did not seem to play an important role in the aetiology of ALL. Interestingly, the risk associated with NAT2 slow-acetylators was most apparent among males homozygous for NAT1*4 (OR=3.3) whereas girls carrying the CYP1A1*4 allele were significantly underrepresented in the patient group (OR=0.2). These findings point to a gender-specific effect of DNA variants which, at least in part, may explain why ALL is more prevalent among boys. To assess gene-gene interactions, NAT2 slow-acetylators were considered together with GSTM1 null genotypes and CYP1A1*2A alleles. The combined presence of two risk-elevating genotypes appeared to confer an increased risk of ALL among the carriers (OR=2.6). This risk was increased further (OR=3.3) when all three genotypes occurred in the same individuals indicating that the combination of susceptibility variants is more predictive of risk then either of them independently. The association of leukemogenesis in children with metabolising gene variants suggests causal relation to environmental exposures.

Adult↗

PubMed2000

Genetic polymorphisms of N-acetyltransferases 1 and 2 and gene-gene interaction in the susceptibility to childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. In utero and postnatal exposures to various carcinogens may play a role in the etiology of this disease. N-acetyltransferases, encoded by the NAT1 and NAT2 genes are involved in the biotransformation of aromatic amines present in tobacco smoke, environment, and diet. Their rapid and slow acetylation activity alleles have been shown to modify the risk to a variety of solid tumors in adults. To investigate the role of NAT1 and NAT2 variants as risk-modifying factors in leukemogenesis, we conducted a case-control study on 176 ALL patients and 306 healthy controls of French-Canadian origin. Slow NAT2 acetylation genotype was found to be a significant risk determinant of ALL (odds ratio, 1.5; 95% confidence interval, 1.0-2.2) because of overrepresentation of the alleles NAT2*5C and *7B and underrepresentation of NAT2*4. Besides a slight increase in NAT1*4 allele frequency among cases, no independent association of NAT1 acetylation genotypes and ALL risk was observed. However, the risk associated with NAT2 slow acetylators was more apparent among homozygous individuals for NAT1*4 (odds ratio, 1.9; 95% confidence interval, 1.1-3.4). When NAT2 slow acetylators were considered together with the other risk-elevating genotypes, GSTM1 null and CYP1A1*2A, the risk of ALL increased further, which showed that the combination of these genotypes is more predictive of risk then either of them independently. These findings suggest that leukemogenesis in children is associated with carcinogen metabolism and consequently related to environmental exposures.

Acetyltransferases↗

PubMed1999

Rapid detection of CYP1A1, CYP2D6, and NAT variants by multiplex polymerase chain reaction and allele-specific oligonucleotide assay.

Drugs and carcinogens are excreted from the body after metabolic conversion involving enzymes mediating oxidative metabolism and conjugation. Many of the corresponding genes exhibit functional polymorphisms that contribute to individual cancer susceptibility. To increase the efficiency and to facilitate genotyping, we developed a combined approach (PCR-ASO) which includes multiplex PCR and allele-specific oligonucleotide (ASO) hybridization. PCR primer pairs were used to amplify the following alleles/variants: CYP1A1*1, *2A, *2B; CYP2D6*3, *4; NAT1*4, *3, *10, *11, *14, *15; and NAT2*4, *5A, *5B, *5C, *6A, *7B. The products were dot-blotted and polymorphisms were detected by hybridization with ASO probes for both wild-type and variant sites in parallel. This approach was validated by genotyping DNA samples from a French-Canadian population that was previously analyzed by PCR-RFLP. The variants frequencies were compared with the data on other populations available in the literature. The PCR-ASO assay appears to be simple, efficient, and cost-effective, particularly if a large number of samples are to be screened for several DNA variants. This approach has potential for automation with microplates and robotic workstations for high throughput.

Arylamine N-Acetyltransferase↗

PubMed1999

CORE-SINEs: eukaryotic short interspersed retroposing elements with common sequence motifs.

A 65-bp "core" sequence is dispersed in hundreds of thousands copies in the human genome. This sequence was found to constitute the central segment of a group of short interspersed elements (SINEs), referred to as mammalian-wide interspersed repeats, that proliferated before the radiation of placental mammals. Here, we propose that the core identifies an ancient tRNA-like SINE element, which survived in different lineages such as mammals, reptiles, birds, and fish, as well as mollusks, presumably for >550 million years. This element gave rise to a number of sequence families (CORE-SINEs), including mammalian-wide interspersed repeats, whose distinct 3' ends are shared with different families of long interspersed elements (LINEs). The evolutionary success of the generic CORE-SINE element can be related to the recruitment of the internal promoter from highly transcribed host RNA as well as to its capacity to adapt to changing retropositional opportunities by sequence exchange with actively amplifying LINEs. It reinforces the notion that the very existence of SINEs depends on the cohabitation with both LINEs and the host genome.

Animals↗

PubMed1999

Susceptibility to childhood acute lymphoblastic leukemia: influence of CYP1A1, CYP2D6, GSTM1, and GSTT1 genetic polymorphisms.

Although acute lymphoblastic leukemia (ALL) is the most common childhood cancer, factors governing susceptibility to this disease have not yet been identified. As such, ALL offers a useful opportunity to examine the glutathione S-transferase and cytochrome P450 genes in determining susceptibility to pediatric cancers. Both enzymes are involved in carcinogen metabolism and have been shown to influence the risk a variety of solid tumors in adults. To determine whether these genes played a similar role in childhood leukemogenesis, we compared the allele frequencies of 177 childhood ALL patients and 304 controls for the CYP1A1, CYP2D6, GSTM1, and GSTT1 genes. We chose the French population of Quebec as our study population because of its relative genetic homogeneity. The GSTM1 null and CYP1A1*2A genotypes were both found to be significant predictors of ALL risk (odds ratio [OR] = 1.8). Those possessing both genotypes were at an even greater risk of developing the disease (OR = 3.3). None of the other alleles tested for proved to be significant indicators of ALL risk. Unexpectedly, girls carrying the CYP1A1*4 were significantly underrepresented in the ALL group (OR = 0.2), suggesting that a gender-specific protective role exists for this allele. These results suggest that the risk of ALL may indeed be associated with xenobiotics-metabolism, and thus with environmental exposures. Our findings may also explain, in part, why ALL is more prevalent among males than females.

Adolescent↗

PubMed1999

Phylogenetic affinities of tarsier in the context of primate Alu repeats.

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.

Alu Elements↗

PubMed1999

Frequent loss of heterozygosity at the DNA mismatch-repair loci hMLH1 and hMSH3 in sporadic breast cancer.

To study the involvement of DNA mismatch-repair genes in sporadic breast cancer, matched normal and tumoral DNA samples of 22 patients were analysed for genetic instability and loss of heterozygosity (LOH) with 42 microsatellites at or linked to hMLH1 (3p21), hMSH2 (2p16), hMSH3 (5q11-q13), hMSH6 (2p16), hPMS1 (2q32) and hPMS2 (7p22) loci. Chromosomal regions 3p21 and 5q11-q13 were found hemizygously deleted in 46% and 23% of patients respectively. Half of the patients deleted at hMLH1 were also deleted at hMSH3. The shortest regions of overlapping (SRO) deletions were delimited by markers D3S1298 and D3S1266 at 3p21 and by D5S647 and D5S418 at 5q11-q13. Currently, the genes hMLH1 (3p21) and hMSH3 (5q11-q13) are the only known candidates located within these regions. The consequence of these allelic losses is still unclear because none of the breast cancers examined displayed microsatellite instability, a hallmark of mismatch-repair defect during replication error correction. We suggest that hMLH1 and hMSH3 could be involved in breast tumorigenesis through cellular functions other than replication error correction.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Spatial and temporal distribution of the neutral polymorphisms in the last ZFX intron: analysis of the haplotype structure and genealogy.

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.

DNA-Binding Proteins↗

PubMed1999

Is selection responsible for the low level of variation in the last intron of the ZFY locus?

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.

Base Sequence↗