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Our survey sought to establish an overview of French practice with respect to prescribing Yq deletion screening and molecular diagnostic methods, and to answer the following points. Our objectives are to give a technical, financial overview of Y chromosome microdeletion screening issues. Two questionnaires were drawn up, one for prescribers and the other for molecular biologists.

Survey objectives were explained in an accompanying letter. Thirty of the 72 centres did not prescribe microdeletion screening nine public, 20 private and one mixed centre.

Y-chromosomal DNA analysis in French male lineages.

Response rates were not significantly different between public and private centres. From the IVF centre responses, 30 laboratories performing molecular biology analysis were identified. Questions of technique or lack of consensus as to the choice of markers were rarely suggested as reasons for not carrying out microdeletion screening. It is worth recalling that the diagnosis of a Y chromosome microdeletion does, as a matter of fact, affect patient management, because freezing of sperm for preventive purposes has been proposed since Krausz et al. Moreover, a positive diagnosis of microdeletion is of prognostic value for the indications for testicular biopsy according to the type of microdeletion found Brandell et al.

Furthermore, preventive therapy sperm cryoconservation for successive assisted reproductive techniques could be proposed to affected sons, as suggested by previous studies Krausz and McElreavey, ; Toth et al. It should also be mentioned that the detection of nullisomic gametes for the sex chromosomes in patients with microdeletions Siffroi et al. The converse has also been demonstrated recently: Thus, these theories are still controversial.

We can only speculate that it may be a reflection of the lack of available treatment in cases of azoospermia. Eight centres did not consider oligozoospermia to be an indication. The reason for these limitations is unclear. Another surprising result was that four centres paradoxically considered the notion of familial infertility as a prime indication for this investigation, although microdeletions in point of fact appear de novo in the great majority of cases.

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In parallel with prescribing centres, the number of laboratories carrying out this analysis is steadily increasing Figure 3. The overall activities of each laboratory since analysis began are shown in Figure 4. Our survey revealed an extreme diversity of practice: Three laboratories analysed their markers by a simplex technique alone. Fourteen laboratories carried out a preliminary investigation with a limited number of markers and, in a second step, refined the deletion limits and extent with a series of supplementary markers.

The number of markers used for first intention screening, and in second intention, to determine the deletion extent, varied greatly from one centre to another Figure 5. Eight laboratories performed the diagnosis without specifying the extent of the microdeletion detected. However, it must be kept in mind that this survey was conducted in , before the refined map of the Y chromosome was published Skaletsky et al.

On the other hand, fine definition of the breakpoints of the AZFa, AZFb and AZFc regions with the introduction of new markers will allow the selection of new second step markers Saxena et al. Control genes used also greatly varied from one centre to another: Unlike all other chromosomes, which we have two copies of in each of our cells, Y chromosomes are only ever present as a single copy, passed from fathers to their sons.

The degrading human Y

Deprived of the benefits of recombination, Y chromosomal genes degenerate over time and are eventually lost from the genome. Looking to other species Y chromosomes exist in mammals and some other species , a growing body of evidence indicates that Y-chromosome gene amplification is a general principle across the board. These amplified genes play critical roles in sperm production and at least in rodents in regulating offspring sex ratio.

Writing in Molecular Biology and Evolution recently, researchers give evidence that this increase in gene copy number in mice is a result of natural selection. The latter group argues that its defence mechanisms do a great job and have rescued the Y chromosome. But the leavers say that all they are doing is allowing the Y chromosome to cling on by its fingernails, before eventually dropping off the cliff. The debate therefore continues. A leading proponent of the leave argument, Jenny Graves from La Trobe University in Australia, claims that, if you take a long-term perspective, the Y chromosomes are inevitably doomed — even if they sometimes hold on a bit longer than expected.

In a paper, she points out that Japanese spiny rats and mole voles have lost their Y chromosomes entirely — and argues that the processes of genes being lost or created on the Y chromosome inevitably lead to fertility problems. This in turn can ultimately drive the formation of entirely new species.

As we argue in a chapter in a new e-book , even if the Y chromosome in humans does disappear, it does not necessarily mean that males themselves are on their way out. Even in the species that have actually lost their Y chromosomes completely, males and females are both still necessary for reproduction.

Sex in other vertebrates

The deep-rooting markers SRYa, M9, 92R7, YAP and 12f2q were typed in all samples and, in some cases, the remaining markers were typed hierarchically; e. Intra-population diversity was measured through the gene diversity index Nei as shown in table I. Inter-population diversity was calculated through conventional F-statistics Wright Two measures of differentiation are provided: A group of reference samples table III, IV was designated according to geographic criteria as follows: A matrix of F CT values concerning the four Jerban samples and these groups was computed to identify the putative mother population of each Jerban sample table III.

The PCA method involves a mathematical procedure that transforms a number of possibly correlated variables into a smaller number of uncorrelated variables called principal components. The first principal component accounts for as much of the variability in the data as possible, and each succeeding component accounts for as much of the remaining variability as possible.

The analysis was performed with the Excel applet GenAlEx by Peakall and Smouse freely available at the following Internet address: The first result concerns the total homogeneity of the Jewish group where all the 34 typed individuals share the same haplogroup Hg J that is also present, at a very low frequency 4.

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  • This haplogroup presents its highest frequencies in the Fertile Crescent and has been suggested to be a genetic signature of migrations from the Middle East in Neolithic and post-Neolithic times Semino et al. High frequencies of this lineage are recorded in the Jerban Berbers This haplogroup shows its highest frequencies in North Africa. Hg P xR1a, R1b3f lineage has been found predominantly in Europe, showing increasing frequencies from the Middle East to north-western Europe Semino et al.

    However, little information can be deduced from this latter lineage since it is present in both Europe and Asia and does not show any informative geographic variation in the Eurasian landscape. Given the little information conveyed by a single Y-chromosome we will not discuss it further in this context.

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    Hg A and Hg E3a are found at high frequency in sub-Saharan African lineages and they have been suggested to be genetic signatures of Khoisan and Bantu language families, respectively. They have never been recorded outside Africa Hammer et al. Berbers show an intermediate level of genetic diversity with a fairly low level of variability. F ST distance measures table II give an overall view of the genetic difference existing among the four Jerban samples.

    In the first column the old and new Y-Chromosome Consortium ; Jobling, Tyler-Smith nomenclature are provided. Table II—Genetic distances computed between the different ethnic groups of the island of Jerba are summarized. Unlike the present study the Jewish sample was always missing in previous studies. Each matrix is based on a different marker. Further details about the sampling strategy adopted can be found in the original publications.

    Results suggest a north African origin for the Arab and Berber samples. Nevertheless, since we had no intermediate populations between Egypt and Algeria, we decided to include Egypt with the Middle Eastern group since the sample comes from the Cairo area. Groups of reference samples table IV were designed according to geographic criteria as follows: A matrix of FCT values concerning the four Jerban samples and these groups was computed to identify the putative ancestral population of each Jerban sample.

    These populations also appear in the PCA plot of figure 1. This close correspondence between some of the reference populations and our samples is lost for the Jerban Jewish samples. The Jerban Jews appear to cluster together with other Middle Eastern populations Palestine, Lebanon, Syria , nevertheless they are plotted far apart from them. This feature could be explained by the fact that Jerban Jews encountered a significant bottleneck that is mirrored by allelic profiles and diversity values.

    F ST accounts for genetic distance between samples.

    Haplogroupes Y-ADN par pays

    For a better display both axes are rotated upside-down visible in the direction of the arrows. Percentage of variation explained by the first 3 axes: It can be noted that, if we only sampled a small enough section of the gradient, the data might be linear enough to allow the use of PCA. The horseshoe effect happens because genetic variables, like most environmental variables, can be monotonically related to underlying factors and to each other as is expected in close populations exchanging migrants.