Sex-specific selection on the human X chromosome?

Genes involved in major biological functions, such as reproductive or cognitive functions, are choice targets for natural selection. However, the extent to which these genes are affected by selective pressures remains undefined. The apparent clustering of these genes on sex chromosomes makes this genomic region an attractive model system to study the effects of evolutionary forces. In the present study, we analysed the genetic diversity of a X-linked microsatellite in 1410 X-chromosomes from 10 different human populations. Allelic frequency distributions revealed an unexpected discrepancy between the sexes. By evaluating the different scenarios that could have led to this pattern, we show that sex-specific selection on the tightly linked VCX gene could be the most likely cause of such a distortion.     

Is a gene for microcephaly located on chromosome 1?

Summary A 3-month-old boy with true microcephaly showed the same balanced reciprocal translocation 1q4p as his carrier mother. This reciprocal translocation had been transmitted for at least four generations. Different banding techniques allowed one to describe the rearrangement as: rcp t(1;4)(1pter 1q31::4p161 4pter; 4qter 4p153::1q321 1qter). On the other hand, the proband's father seemed to be a border-line mentally retarded and one of his relatives suffered from mental retardation of unknown origin. Taking into account all these results together with the current literature, it was concluded that the microcephaly appearing in our case could be due to the following two facts: (a) the father was an heterozygote for the gene for microcephaly, and (b) damage or a minute deletion on chromosome 1 between 1q31 and 1q321 bands could occur in the mother's family resulting in a mutation for microcephaly. If this was so, the gene for microcephaly should be located on chromosome 1 at the level of the 1q31–1q321 junction.     

Sublocalization of the human protein C gene on chromosome 2q13–q14

Summary The localization of human protein C gene on chromosome 2 was investigated by in situ hybridization using a partial cDNA for protein C. Silver-grain analysis indicates that the protein C gene is located on 2q13-q14.     

How did the guppy Y chromosome evolve?

The sex chromosome pairs of many species do not undergo genetic recombination, unlike the autosomes. It has been proposed that the suppressed recombination results from natural selection favouring close linkage between sex-determining genes and mutations on this chromosome with advantages in one sex, but disadvantages in the other (these are called sexually antagonistic mutations). No example of such selection leading to suppressed recombination has been described, but populations of the guppy display sexually antagonistic mutations (affecting male coloration), and would be expected to evolve suppressed recombination. In extant close relatives of the guppy, the Y chromosomes have suppressed recombination, and have lost all the genes present on the X (this is called genetic degeneration). However, the guppy Y occasionally recombines with its X, despite carrying sexually antagonistic mutations. We describe evidence that a new Y evolved recently in the guppy, from an X chromosome like that in these relatives, replacing the old, degenerated Y, and explaining why the guppy pair still recombine. The male coloration factors probably arose after the new Y evolved, and have already evolved expression that is confined to males, a different way to avoid the conflict between the sexes.     

DNA polymorphism in the 5′ flanking region of the human carbonic anhydrase II gene on chromosome 8

Summary A restriction-fragment-length polymorphism (RFLP) is described which is associated with the human carbonic anhydrase II gene (CA2) that codes for one of the three genetically distinct carbonic anhydrase isozymes, CA I, CA II, and CA III. The isolated DNA was cleaved with several restriction enzymes and subjected to Southern blot hybridization analysis using a DNA probe containing the 5 end of the human CA II gene. A two allele RFLP which was detected with the restriction endonuclease, Taq I, is expressed phenotypically on Southern blots as either a 5.4 kilobase (kb) fragment or as 4.0 and 1.4 kb fragments. These fragments result from the presence or absence of a Taq I recognition site in the 5 flanking region approximately 1.0kb from the initiation codon of the CA II gene. Segregation analysis showed that the alleles are inherited in a Mendelian fashion, with a frequency of 50%.     

The gene encoding the large human neurofilament subunit (NF-H) maps to the q121–q131 region on human chromosome 22

Summary Using a rat cDNA probe encoding for the C-terminal textension of the large neurofilament subunit (NF-H), we have assigned, by in situ hybridization, the human NF-H gene to the q121–q131 region of chromosome 22. This localization may have implications in neurological diseases such as meningioma where a recessive locus involved in oncogenesis is located within this region.     

Localization of the α2-macroglobulin gene and Lpm gene family on mink chromosome 9

Summary Using cloned cDNA for human ₂-macroglobulin (A2M) as a probe, mink-Chinese hamster hybrid cells were analysed. The results allowed us to assign a gene for A2M to mink chromosome 9. Breeding tests demonstrated that the Lpm-locus coding for other related -macroglobulin protein and the gene for peptidase B (PEPB) are linked 11±3 cm apart. The PEPB gene is located on mink chromosome 9, and hence, the Lpw-locus is on the same mink chromosome. The relationship of the genetic systems controlling the isotypically different -macroglobulins in mink serum are discussed.     

Does human oocyte cryopreservation affect equally on embryo chromosome aneuploidy?

Oocytes cryopreservation as an important part of assisted reproductive technologies, which should ensure after warming not only intact oocyte morphological characteristics, but also their genetic apparatus stability. However, the meiotic spindle is very sensitive to the temperature fluctuations that can lead to unequal chromosome segregation during meiosis and as a consequence can cause embryo aneuploidy after oocyte fertilization. The aim of the study was to estimate the oocytes cryopreservation impact on human embryo chromosome aneuploidy. It has been shown that fertilization rate of the cryopreserved oocytes did not differ from fresh ones (83.1% vs 84% respectively). The number of blastocysts obtained from cryopreserved oocytes was less than that obtained from fresh oocytes, however, their morphological characteristics were better if compared the fresh oocytes. Our results showed different cryopreservation impact on aneuploidy rates of certain chromosomes in embryos obtained from cryopreserved oocytes. They had an increased aneuploidy of chromosome 13 and a decreased nondisjunction of chromosome 18 and sex chromosomes.     

Is the mission to identify all the human proteins achievable? —Commenting on the human proteome draft maps

<正>Unveiling the structure and function of all the proteins a human body produces is undoubtedly a key task for us to better understand ourselves.Although a mission difficult to achieve,this apparently becomes more feasible upon the determination of the DNA sequence of the whole human genome,which was predicted to encode a total of20,000–25,000 proteins[1].Recent efforts of direct(de no-     

Y chromosome and male infertility: what is a normal Y chromosome?

The human Y chromosome contains a number of genes and gene families that are essential for germ cell development and maintenance. Many of these genes are located in highly repetitive elements that are subject to rearrangements. Deletion of azoospermia factor (AZF) regions AZFa, AZFb, and AZFc are found in approximately 10-15% of men with severe forms of spermatogenic failure. Several partial AZFc deletions have been described. One of these, which removes around half of all the genes within the AZFc region, appears to be present as an inconsequential polymorphism in populations of northern Eurasia. A second deletion, termed gr/gr, also results in the absence of several AZFc genes and it may be a genetic risk factor for spermatogenic failure. However, the link between these partial deletions and fertility is unclear. The gr/gr deletion is not a single deletion but a combination of deletions that vary in size and complexity and result in the absence of different genes. There are also regional or ethnic differences in the frequency of gr/gr deletions. In some Y-chromosome lineages, these deletions appear to be fixed and may have little influence on spermatogenesis. Most of these data (gene content and Y chromosome structure) have been deduced from the reference Y chromosome sequence deposited in NCBI. However, recently there have been attempts to define these types of structural rearrangements in the general population. These have highlighted the considerable degree of structural diversity that exist. Trying to correlate these changes with the phenotypic variability is a major challenge and it is likely that there will not be a single reference (or normal) Y chromosome sequence but many.     

Is the aneuploid chromosome in an apomictic Boechera holboellii a genuine B chromosome?

The Boechera holboellii complex comprises B. holboellii and B. drummondii, both of which can reproduce through sex or apomixis. Sexuality is associated with diploidy, whereas apomictic individuals can either be diploid, aneuploid or triploid. Aneuploid individuals are found in geographically and genetically distinct populations and contain a single extra chromosome. It is unknown whether the supernumerary chromosomes are shared by common descent (single origin) or have originated via introgressive hybridizations associated with the repeated transition from diploidy to triploidy. Diploid plants containing the extra chromosome(s) reproduce apomictically, suggesting that the supernumerary elements are associated with apomixis. In this study we compared flow cytometry data, chromosome morphology, and DNA sequences of sexual diploid and apomictic aneuploids in order to establish whether the extra chromosome fits the classical concept of a B chromosome. Karyotype analyses revealed that the supernumerary chromosome in the metaphase complement is heterochromatic and often smaller than the A chromosomes, and differs in length between apomictic plants from different populations. DNA sequence analyses furthermore demonstrated elevated levels of non-synonymous substitutions in one of the alleles, likely that on the aneuploid chromosome. Although the extra chromosome in apomictic Boechera does not go through normal reductional meiosis, in which it may get eliminated or accumulated by a B-chromosome-specific process, its variable size and heterochromatic nature does meet the remaining criteria for a genuine B chromosome in other species. Its prevalence and conserved genetic composition nonetheless implies that this chromosome, if truly a B, may be atypical with respect to its influence on its carriers.     

An α-fucosidase pseudogene on human chromosome 2

Summary In Chinese hamster-human hybrids with overlapping translocations, the major site of hybridization of a cDNA clone for the liver form of human -l-fucosidase was 1p36.31p34, consistent with hybridization to the FUCA1 locus. No hybridization to the FUCA2 locus on chromosome 6 was observed. Hybridization to a genomic sequence on chromosome 2 was, however, detected, thus defining a new FUCA-like locus. The restriction map of the -fucosidase cDNA could be exactly superimposed upon its region of homology within a genomic clone containing this FUCA-like locus, suggesting that it is a processed pseudogene.     

＂Micro-deletions＂ of the human Y chromosome and their relationship with male infertility

The Y chromosome evolves from an autochromosome and accumulates male-related genes including sex-determining region of Y-chromosome (SRY) and several spermatogenesis-related genes.The human Y chromosome (60 Mb long) is largely composed of repeti-tive sequences that give it a heterochromatic appearance,and it consists of pseudoautosomal,euchromatic,and heterochromatic regions.Located on the two extremities of the Y chromosome,pseudoautosomal regions 1 and 2 (PAR1 and PAR2,2.6 Mb and 320 bp long,re-spectively) are homologs with the termini of the X chromosome.The euchromatic region and some of the repeat-rich heterochromatic parts of the Y chromosome are called "male-specific Y" (MSY),which occupy more than 95% of the whole Y chromosome.After evolu-tion,the Y chromosome becomes the smallest in size with the least number of genes but with the most number of copies of genes that are mostly spermatogenesis-related.The Y chromosome is characterized by highly repetitive sequences (including direct repeats,inverted repeats,and palindromes) and high polymorphism.Several gene rearrangements on the Y chromosome occur during evolution owing to its specific gene structure.The consequences of such rearrangements are not only loss but also gain of specific genes.One hundred and fifty three haplotypes have been discovered in the human Y chromosome.The structure of the Y chromosome in the GenBank belongs to haplotype R1.There are 220 genes (104 coding genes,111 pseudogenes,and 5 other uncategorized genes) according to the most recent count.The 104 coding genes encode a total of about 48 proteins/protein families (including putative proteins/protein families).Among them,16 gene products have been discovered in the azoospermia factor region (AZF) and are related to spermatogenesis.It has been dis-covered that one subset of gene rearrangements on the Y chromosome,"micro-deletions",is a major cause of male infertility in some populations.However,controversies exist about different Y chromosome haplotypes.Six AZFs of the Y chromosome have been discov-ered including AZFa,AZFb,AZFc,and their combinations AZFbc,AZFabc,and partial AZFc called AZFc/gr/gr.Different deletions in AZF lead to different content spermatogenesis loss from teratozoospermia to infertility in different populations depending on their Y hap-lotypes.This article describes the structure of the human Y chromosome and investigates the causes of micro-deletions and their relation-ship with male infertility from the view of chromosome evolution.After analysis of the relationship between AZFc and male infertility,we concluded that spermatogenesis is controlled by a network of genes,which may locate on the Y chromosome,the autochromosomes,or even on the X chromosome.Further investigation of the molecular mechanisms underlying male fertility/infertifity will facilitate our knowledge of functional genomics.     

Mapping of the gene for anti-müllerian hormone to the short arm of human chromosome 19

The gene coding for human anti-Müllerian hormone (AMH) was localized to subbands p13.2----p13.3 on chromosome 19, using in situ hybridization and Southern blot analysis of a panel of man-mouse and man-hamster somatic cell hybrids.     

Human evolution: how recent were the Y chromosome ancestors?

Recent findings of low sequence variability of Y chromosome genes has led to suggestions that the most recent ancestor of human Y chromosomes existed around 50,000 years ago and human population size expanded about 28,000 years ago. But what level of confidence can we have in these estimates?     

Assignment of the gene for carboxypeptidase A to human chromosome 7q22→qter and to mouse chromosome 6

Summary A rat cDNA probe for preprocarboxypeptidase A was used to follow the segregation of the human gene for carboxypeptidase A (CPA) in 49 human x mouse somatic cell hybrids using Southern filter hybridization techniques. CPA was assigned to human chromosome 7q22qter. Similarly, the probe was used to follow the segregation of the mouse gene for carboxypeptidase A (Cpa) in 19 mouse x Chinese hamster somatic cell hybrids. Cpa was assigned to mouse chromosome 6. The gene for carboxypeptidase A forms part of a syntenic group that is conserved in man and mouse.Preliminary chromosomal assignments of carboxypeptidase A in man and mouse have been made in abstract (Honey et al. 1983a, b)