1: Novartis Found Symp. 2005;268:20-33; discussion 33-41, 96-9. Aggressive behaviour: contributions from genes on the Y chromosome. Lovell-Badge R. Division of Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 IAA, UK. The Y-linked gene SRY initiates male development in mammals through a pathway of gene activity leading to testis development. The testis then exports the male signal to the rest of the embryo via secreted molecules such as testosterone. These subsequently lead to many male characteristics in terms of anatomy, physiology and behaviour. Because males tend to be more aggressive than females, and androgens are often blamed for this, SRY can be thought of as a contributor to such behaviour. However, any effect the gene has is very indirect. Nevertheless, accumulating evidence suggests that other sex-linked genes may have more direct effects on differences between the sexes, and some of these are likely to include behavioural phenotypes. While it is not yet clear how important these are, they could compound decisions when treating cases of sex reversal and intersex conditions. They should also be borne in mind as a source of genetic variation when looking at differences between individuals, including behavioural traits such as aggression. Publication Types: Review Review, Tutorial PMID: 16206873 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 2: Neuroscience. 2003;116(1):71-5. Sex differences in mouse cortical thickness are independent of the complement of sex chromosomes. Markham JA, Jurgens HA, Auger CJ, De Vries GJ, Arnold AP, Juraska JM. Department of Psychology, University of Illinois at Urbana-Champaign, Champaign, IL 61820, USA. Although the morphology of the cerebral cortex is known to be sexually dimorphic in several species, to date this difference has not been investigated in mice. The present study is the first to report that the mouse cerebral cortex is thicker in males than in females. We further asked if this sex difference is the result of gonadal hormones, or alternatively is induced by a direct effect of genes encoded on the sex chromosomes. The traditional view of mammalian neural sexual differentiation is that androgens or their metabolites act during early development to masculinize the brain, whereas a feminine brain develops in the relative absence of sex steroids. We used mice in which the testis determination gene Sry was inherited independently from the rest of the Y chromosome to produce XX animals that possessed either ovaries or testes, and XY animals that possessed either testes or ovaries. Thus, the design allowed assessment of the role of sex chromosome genes, independent of gonadal hormones, in the ontogeny of sex differences in the mouse cerebral cortex. When a sex difference was present, mice possessing testes were invariably masculine in the morphology of the cerebral cortex, independent of the complement of their sex chromosomes (XX vs. XY), and mice with ovaries always displayed the feminine phenotype. These data suggest that sex differences in cortical thickness are under the control of gonadal steroids and not sex chromosomal complement. However, it is unclear whether it is the presence of testicular secretions or the absence of ovarian hormones that is responsible for the thicker male cerebral cortex. Copyright 2003 IBRO PMID: 12535939 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 3: Am J Med Genet. 2002 Jun 15;110(2):122-30. Anorectal anomalies associated with or as part of other anomalies. Cuschieri A; EUROCAT Working Group. Department of Anatomy, University of Malta, Msida. acus1@um.edu.mt Anorectal anomalies occurring with other anomalies or as part of syndromes were analyzed to determine how their epidemiological characteristics differed from those of isolated anal anomalies. Almost 15% of cases were chromosomal, monogenic or teratogenic syndromes, whereas the rest were of unknown cause including sequences (9.3%), VACTERL associations (15.4%) and multiple congenital anomalies (MCA) (60.2%). Almost half of babies with MCA had one or two VACTERL anomalies with distribution frequencies that did not differ significantly from those in babies with the full VACTERL association. There were considerable differences in the frequency of the VACTERL association among babies with different types of anorectal anomaly. Babies with anal anomalies occurring with sequences, VACTERL or MCA showed the same sex differences as babies with isolated anal anomalies, namely male predominance in anal atresia without fistula or cloaca, no sex difference in anal atresia with fistula, and female predominance in ectopic anus and congenital anal fistula. These anomalies, however, were associated with significantly lower mean gestational lengths and birth weights, and higher frequencies of fetal death and pregnancy termination than babies with isolated anal anomalies. Twins were more frequent in sequences, VACTERL and MCA than in isolated anomalies, monogenic syndromes or chromosome anomalies. Five cases were conjoined twins, representing 15% of all cases of twin pregnancies with an anal anomaly. Indeterminate sex was more frequent in babies with anal atresias without fistula than in those with fistula. Anal anomalies are defects of blastogenesis attributable to disorders in expression of pattern determining genes. The differential sex involvement in different types of anal anomaly may be manifestations of expression of the HY/SRY genes during blastogenesis or of X-linkage. Copyright 2002 Wiley-Liss, Inc. PMID: 12116249 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 4: Theriogenology. 2002 Mar 1;57(4):1327-46. Collection frequency affects percent Y-chromosome bearing sperm, sperm head area and quality of bovine ejaculates. Chandler JE, Canal AM, Paul JB, Moser EB. Department of Diary Science, Agricultural Experiment Station, Louisiana State University Agricultural Center, Baton Rouge 70803, USA. jchandler@agctr.lsu.edu This study evaluated the percentage of Y-chromosome bearing spermatozoal (%Y-CBS) variation from ejaculates within individual males using two experiments. In the first experiment, six ejaculates were taken from each of five sexually rested (>30 days) Holstein bulls. Ejaculates were processed separately and stored in liquid nitrogen. From each ejaculate, five straws were thawed and equal sperm number, pooled samples were constructed using hemacytometer counts. Individual ejaculate DNA samples were extracted and quantified by spectroscopy. AY-chromosome specific segment was amplified by polymerase chain reaction (PCR) and the product separated by gel electrophoresis. Ethidium bromide stained bands were detected by image analysis and equated to a 50 %Y-CBS pool. In the second experiment (91 days), two ejaculates were collected from sexually rested (>21 days) bulls weekly and two ejaculates were collected from bulls every 21 days. Specific Y-chromosome (SRY) and X-chromosome (factor IX, F9) sperm DNA was amplified by PCR and the products separated by gel electrophoresis. Ethidium bromide stained bands were detected by image analysis and compared to a standard curve constructed from pure SRY and F9 PCR product. The log ratio (SRY/F9) of the corrected intensity densities were used to estimate the percent Y-chromosome DNA bearing spermatozoa (%Y-CDBS) in each ejaculate using inverse regression procedures. In Experiment 1, ejaculate differences for the first collection ranged from 17 to 71 %Y-CBS. Differences remained large for the second ejaculates and lessened for the third and fourth collections. Differences were least for the last two collections. Sperm head area also fluctuated. In Experiment 2, collection frequency affected the pattern of %Y-CDBS response. In bulls collected weekly, %Y-CDBS changed in a sinusoid fashion with a period of about 13.5 days. For bulls collected on a 21-day interval, %Y-CDBS ejaculate differences were high in the first ejaculate after sexual rest. Maximization of %Y-CDBS variation between ejaculate and its identification by PCR would allow ejaculate selection to be used to the alter the sex ratio in producers' calf crops. PMID: 12013453 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 5: Dev Biol. 2000 Mar 15;219(2):277-86. Both nuclear and cytoplasmic components are defective in oocytes of the B6.Y(TIR) sex-reversed female mouse. Amleh A, Smith L, Chen H, Taketo T. Urology Research Laboratory, Department of Surgery, McGill University, Montreal, Quebec, H3A 1A1, Canada. In the mammalian gonadal primordium, activation of the Sry gene on the Y chromosome initiates a cascade of genetic events leading to testicular organization whereas its absence results in ovarian differentiation. An exception occurs when the Y chromosome of Mus musculus domesticus from Tirano, Italy (Y(TIR)), is placed on the C57BL/6J (B6) genetic background. The B6.Y(TIR) progeny develop only ovaries or ovotestes despite Sry transcription in fetal life. Consequently, the XY offspring with bilateral ovaries develop into apparently normal females, but their eggs fail to develop after fertilization. Our previous studies have shown that the primary cause of infertility can be attributed to oocytes rather than their surrounding somatic cells in the XY ovary. This study attempted to identify the defects in oocytes from the B6.Y(TIR) female mouse. We examined the developmental potential of embryos from XY and XX females after exchanging their nuclear components by microsurgery following in vitro maturation and fertilization. The results suggest that both nuclear and cytoplasmic components are defective in oocytes from XY females. In the XY fetal ovary, most germ cells entered meiosis and their autosomes appeared to synapse normally while the X and Y chromosomes remained unpaired during meiotic prophase. This lack of X-Y pairing probably caused aneuploidy in some secondary oocytes following in vitro maturation. However, normal numbers of chromosomes in the rest of the secondary oocytes indicate that aneuploidy alone can not explain the nuclear defect in oocytes. Copyright 2000 Academic Press. PMID: 10694422 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 6: J Exp Zool. 1999 Oct 15;285(3):197-214. Some remarks on the female and male Keimbahn in the light of evolution and history. Hilscher W. Heinrich Heine University, Duesseldorf, D-40225 Germany. From the existence of two types of cells for reproduction-the female and male germ cells (GCs)-and by recombination of the genome, evolution proceeded dramatically. Unicellular and multicellular plants frequently are characterized by a sequence of haploid and diploid phases, or generations, with gametes and spores as reproductive cells. Isogamy, anisogamy, and oogamy can be distinguished depending on the GCs that correspond, differ in size, or impose as egg cell and sperm cell. In protozoans, too, species are found in which GCs differ clearly from each other. In the female lineage of angiosperms, a "Keimbahn chain" consisting of five successive germ line cells can be observed. Oogenesis and spermatogenesis are complete in coelenterates and similar in mammals. However, the controlling mechanisms are by far more complex in the latter. This means that the balance of hormonal and vegetative nervous influences (stimulation, inhibition) on gametogenesis is not primarily orientated on the germ line cells themselves, but mostly on the structural and functional situation of the gonads and the individual carriers. This becomes particularly evident in insects, where gametogenesis, on the one side, depends on the development of the rest of the organism but on the other side represents an independent developmental process. The point at which germ line cells and somatic cells separate correlates more or less with the degree of phylogenetic development. In worms, insects, and up to the anurans, a part of the cytoplasm, the so-called germ plasma, is separated for the development of GCs during oogenesis (preformistic development). However, in urodeles, reptiles, birds, and mammals, GCs and somatic cells cannot be distinguished before gastrulation (epigenetic development). In various species (e.g., in some oligochaetes and snails), there exist "double spermatogenic lines." In mammals (probably in other vertebrates and perhaps in various phyla of animals, too), the female Keimbahn is provided with only one proliferation system. The male gametogenesis is equipped with two systems: the first corresponds to the female germ line, the second is responsible for the immense number of gametes produced in the mature testes. In mammals the message to become male lies on the Y-chromosome (on its short arm in man and mouse) and was identified as the gene SRY in human and Sry in mouse. The fertility genes that are responsible for an uninterrupted spermatogenesis, up to fertilizing spermatozoa, are sitting on the long arm of the human Y-chromosome. J. Exp. Zool. (Mol. Dev. Evol.) 285:197-214, 1999. Copyright 1999 Wiley-Liss, Inc. Publication Types: Historical Article Review PMID: 10497319 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 7: Cytogenet Cell Genet. 1997;79(3-4):167-71. Multiple, polymorphic copies of SRY in both males and females of the vole Microtus cabrerae. Bullejos M, Sanchez A, Burgos M, Hera C, Jimenez R, Diaz de la Guardia R. Departamento de Genetica, Facultad de Ciencias, Universidad de Granada, Spain. In mammals, sex determination is controlled by the Y-linked gene SRY. Although SRY is male-specific in most eutherian and marsupial species, with a single copy on the Y chromosome, several rodent species have multiple Y-linked copies of SRY, and two mole-vole species of the genus Ellobius determine sex without the Y chromosome or the SRY gene. We searched for homologs of SRY in three vole species of the genus Microtus and concluded that this gene is not male-specific in M. cabrerae, as it is present in multiple, polymorphic copies in both males and females. In contrast, SRY is male-specific in the related species M. agrestis and M. nivalis. Up to 15 different partial sequences of the SRY gene were found in M. cabrerae. Southern blots suggest that most of the extra copies of SRY are X-linked. One of the copies observed only in males has a sequence identical to that of the SRY gene in M. agrestis and may represent a functional copy of the gene in this species. The rest are probably nonfunctional pseudogenes. PMID: 9605842 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 8: Am J Med Genet. 1998 Mar 5;76(2):120-4. Frequency of Y chromosomal material in Mexican patients with Ullrich-Turner syndrome. Lopez M, Canto P, Aguinaga M, Torres L, Cervantes A, Alfaro G, Mendez JP, Kofman-Alfaro S. Servicio de Genetica, Hospital General de Mexico/Facultad de Medicina, UNAM, Mexico City. Cytogenetic studies have shown that 40-60% of patients with Ullrich-Turner syndrome (UTS) are 45,X, whereas the rest have structural aberrations of the X chromosome or mosaicism with a second cell line containing a structurally normal or abnormal X or Y chromosome. However, molecular analysis has demonstrated a higher proportion of mosaicism, and studies in different populations have shown an extremely variable frequency of Y mosaicism of 0-61%. We used Southern blot analysis and polymerase chain reaction (PCR) to detect the presence of Ycen, ZFY, SRY, and Yqh in 50 Mexican patients with UTS and different karyotypes to determine the origin of marker chromosomes and the presence of Y sequences. Our results indicated the origin of the marker chromosome in 1 patient and detected the presence of Y sequences in 4 45,X patients. Taken together, we found a 12% incidence of Y sequences in individuals with UTS. The amount of Y-derived material was variable, making the correlation between phenotype and molecular data difficult. Only 1 patient had a gonadoblastoma. We discuss the presence of Y chromosomes or Y sequences in patients with UTS and compare our frequency with that previously reported. PMID: 9511973 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 9: Mol Reprod Dev. 1996 Jul;44(3):289-94. Females of four mole species of genus Talpa (insectivora, mammalia) are true hermaphrodites with ovotestes. Sanchez A, Bullejos M, Burgos M, Hera C, Stamatopoulos C, Diaz De la Guardia R, Jimenez R. Departamento de Genetica, Facultad de Ciencias, Universidad de Granada, Spain. We studied the anatomical, histological, and genetic features of the sexual tract in four European mole species of the genus Talpa (Insectivora, mammalia): T. occidentalis, T. europaea, T. romana, and T. stankovici. All XY individuals had a normal male phenotype, whereas all XX individuals in all four species had features that identified them as intersexes. These individuals were nonetheless presumed to be functionally fertile females. Intersexuality was manifested mainly as gonadal hermaphroditism, with all females possessing bilateral ovotestes. The gonads were composed of a small portion of histologically normal ovarian tissue and a variably sized, generally large mass of disgenetic testicular tissue, accompanied by a small, rudimentary epididymis. The rest of the sexual tract was typically female, including oviducts, uterus, and vagina of normal appearance. Polymerase chain reaction (PCR) and Southern blotting analyses showed that the mammalian testis-determining gene SRY is present in males but not in females. Part of the conserved sequence of the mole SRY gene was cloned and sequenced after PCR amplification in two of the four mole species (T. occidentalis from Spain and T. romana from Italy). Sequences were identical in these two species and were very similar to those of the human and mouse SRY gene. Our findings constitute the first evidence of the existence of a genus-specific case of true hermaphroditism, probably due to a very ancient mutation that fixed in populations of the ancestral species from which contemporary moles evolved. The possible nature of this mutation is discussed with regard to the cytologic, histologic, and genetic features of the gonads in Talpa females. PMID: 8858598 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 10: Gene. 1995 Feb 14;153(2):275-6. The zebrafish Zf-Sox 19 protein: a novel member of the Sox family which reveals highly conserved motifs outside of the DNA-binding domain. Vriz S, Lovell-Badge R. Unite de genetique des mammiferes, Institut Pasteur, Paris, France. A cDNA encoding a zebrafish Sox protein (Sry-type high-mobility-group box) was isolated and sequenced. The sequence within the HMG box is close to those of the B subfamily comprising mouse Sox-1, Sox-2, Sox-3 and Sox-14. While much of the rest of the zebrafish protein is unique, there are blocks of amino acids showing considerable identity with regions of Sox-1, -2 and -3. These domains may represent conserved parts of the protein, required for interaction with other proteins, and strengthen the assignment of the zebrafish gene, termed Zf-sox 19, to the B subfamily. PMID: 7875601 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 11: Chromosome Res. 1993 Jul;1(2):117-20. Comparative mapping of SRY in the great apes. Toder R, Zeitler S, Goodfellow PN, Schempp W. Institut fur Humangenetik und Anthropologie, Universitat Freiburg, Germany. Cytogenetic studies of the primate Y chromosomes have suggested that extensive rearrangements have occurred during evolution of the great apes. We have used in situ hybridization to define these rearrangements at the molecular level. pHU-14, a probe including sequences from the sex determining gene SRY, hybridizes close to the early replicating pseudoautosomal segment in a telomeric or subtelomeric position of the Y chromosomes of all great apes. The low copy repeat detected by the probe Fr35-II is obviously included in Y chromosomal rearrangements during hominid evolution. These results, combined with previous studies, suggest that the Y chromosome in great apes has a conserved region including the pseudoautosomal region and the testis-determining region. The rest of the Y chromosome has undergone several rearrangements in the different great apes. PMID: 8143095 [PubMed - indexed for MEDLINE] ---------------------------------------------------------------