Abstract: In this paper, we describe the accomplishments of the initial phase of the Human Genome Project, with particular attention to the progress made toward achieving the defined goals for constructing genetic and physical maps of the human genome and determining the sequence of human DNA, identifying the complete set of human genes, and analyzing the need for adequate policies for using the information about human genetics in ways that maximize the benefits for individuals and society.

Abstract: Two closely-linked genes, Ragl and Rag2, are required for the recombination of V, D, and J gene segments to form the genes encoding V regions of Igs and T-cell receptors. In several mammalian species, chickens, and Xenopus laevis, the coding region of RAG1 lies within a single exon; its sequence is highly conserved from amphibians to mammals (Schatz et al. 1992; Oettinger 1992). These features suggest that it may be possible to use the polymerase chain reaction (PCR) with degenerate primers to amplify a segment of Rag1 from genomic DNA of more primitive species. When zebrafish (Danio rerio) DNA was PCR-amplified under conditions similar to those used previously for Xenopus Ragl (Greenhalgh et al. 1993), with the same degenerate primers, a product of expected size [638 base pairs (bp)] was obtained. Although amplification of nurse shark (Ginglymostoma cirratum) DNA yielded no product of this size detectable by ethidium bromide staining, a faint band migrating at the expected position was detected by Southern blotting with a Xenopus Rag1 probe. This product was gel-purified and reamplified with the same reverse primer and a forward primer internal to that used initially: 5 ' -AARATGAARCCNGTNTGG-3' . A product of expected size (359 bp) was obtained. The zebrafish and shark amplification products were cloned and sequenced on both strands. Southern blotting of Eco RI digests of genomic DNA, at high stringency, with probes derived from the cloned zebrafish and shark products revealed bands of N0.9 and 1.0 kb, respectively. Comparison of the nucleotide and predicted amino acid sequences of the zebrafish and shark RAG1 segments with sequences of the corresponding segments of mouse, chicken, and Xenopus Ragl shows a high degree of conservation (Fig. 1). The amino acid sequence encoded by the zebrafish segment is 74%-79% identical to that in Xenopus, chicken, or mouse; in this region the identity among the latter three sequences is 90%. The amino acid sequences corresponding to the shark segment are even more conserved. Particularly striking is the conservation from positions 143 to 186, in which the amino acid sequence of Ragl in all five species is identical except for a single Ile ~ Val replacement in the zebrafish sequence. Relatively little is known about lymphopoeisis in teleosts or elasmobranchs. The availability of specific nucleic acid probes for Ragl in zebrafish and shark should facilitate the identification of sites of V (D) J rearrangement in B and T lymphocytes. Rag1 may also be an indicator of the presence of rearranging immune system genes in cyclostomes, primitive vertebrates in which immunoglobulins and T-cell receptors have not yet been clearly identified. However, our attempts to identify Ragl in lampreys and hagfish by PCR amplification and by Southern blotting have not been successful.

Abstract: Eleven novel mutations were identified in the NF2 tumour suppressor gene in a panel of British NF2 patients. Screening was performed using a combination of heteroduplex and single-strand conformation polymorphism analysis on polymerase chain reaction amplified material.

Abstract: P-element induced double strand break repair in Drosophila can be used for studying the mechanisms of homologous recombination in higher eucaryotes as well as for targeting and converting genes in their original chromosomal environment. So far studies on the molecular mechanisms of recombination were mainly possible in fungi. Even though gene targeting through homologous recombination is becoming a routine instrument in the mouse the underlying molecular events are by no means clear. The genetics of Drosophila provides a powerful tool to study the basics of gene targeting and gene conversion events in higher eucaryotes.

Abstract: The classical conception of the chromosomal mechanism of sex determination presumes a chromosome unique for and determining the heterogametic sex. On the basis of recent evidence, however, this picture is becoming increasingly complex, with a multitude of genes appearing to interact simultaneously or successively to bring about the gonadal phenotype. The genes identified so far that are thought to be involved in the process of human sex determination are distributed on various chromosomes, but the consecution of their function remains to be elucidated. To the Y chromosome only a relative role can be ascribed, and it has not yet been established which gene is on top of the cascade. All of the genes under discussion are involved in transcriptional control, and at least the majority of them appear to exert pleiotropic effects. The regulation of their expression must still be defined, and it will be a long way before a link to gonadal morphogenesis is ultimately found.

Abstract: Species: Human Locus name: Gonadotropin-releasing hormone receptor Locus symbol: GNRHR Map position: Chromosome 4q21.2 Methods of mapping: Fluorescence in situ hybridization (FISH) to normal human lymphocyte chromosomes with a biotinylated probe detected with avidin-fluorescein isothiocyanate (FITC) [1]. Chromosomes were counterstained with propidium iodide and 4',6'diamidin-2-phenyfindol-dihydrochloride (DAPI). Images of metaphase preparations were captured by a thermoelectrically cooled, charge coupled camera (Photometrics, Tucson, Ariz.). Separate images of DAPI-banded chromosomes and of FITC-targeted chromosomes were acquired and merged by use of image analysis software and pseudo-colored blue (DAPI) and yellow (FITC) as described [2] and overlaid electronically. Molecular reagents used.\" A 15-kb )~DNA probe obtained through screening of a human genomic library constructed in FIXII [3]. Results: The regional assignment was determined by the analysis of 20 well-spread metaphases. Positive hybridization signals in the central parts of band 4q21 (4q21.2) were noted in 17 out of 20 cells (85%). Signals were visualized on both homologs in 55% (11/20) of the spreads. The band assignment was determined by measuring the fractional chromosome length and by analyzing the banding pattern generated by the DAPI counterstained image (Fig. 1). Discussion: With PCR amplification of somatic hybrid cell lines, previous data have mapped the GnRH receptor gene to human Chr 4q13.1-q21.1 [4]. This localization was apparently confirmed by the work of Morrison and associates, who used a human 1.9-kb cDNA probe that hybridized to bands 4q13.2-13.3 [5]. However, using a larger genomic clone as a probe and FISH analysis of extended metaphase chromosomes, we have detected hybridization in the adjacent distal band 4q21.2. FISH mapping with metaphase chromosome preparations probably has an accuracy of no more than 4-7 megabases of DNA and is dependent on both the quality of preparation and the probe signal strength. The use of larger genomic probe should, therefore, increase the precision of chromosomal localization. Even though originally recognized as a hypothalamic peptide acting on gonadotrophs, GnRH has been demonstrated to exert direct and receptor-specific effects on both ovary and testis, and the ovarian expression of the GnRH receptor gene is under regulatory influence by gonadotropins [6,7]. The more precise distal chromosomal localization of the GnRH receptor gene will facifitate further studies on possible alterations in its genomic sequence that may have significant implications on fertility.

Abstract: R. MATALON l*, R. KAUL 1, G. E GAO l, K. MICHALS l, R. G. F. Gga'c 2, S. BENNETT-BRITON 3, A. NORMAN 4, M. SMITH 5 and C. JAKOBS 6 1Research Institute, Miami Children's Hospital, USA; 2Children's Hospital, Birmingham, UK; 3Good Hope Hospital, West Midlands, UK; 4Birmingham Maternity Hospital, Birmingham, UK; 5Burton District General Hospital, Birmingham, UK; 6Department of Pediatrics, Free University of Amsterdam, The Netherlands

Abstract: 5S rRNA is one of the two small RNA molecules localized in the large ribosomal subunit and thereby is involved in protein synthesis. 5S rRNAs from many different organisms have been sequenced, and more than 700 5S rRNA transcripts and 5S rRNA gene sequences have been compiled (Specht et al. 1991). The 5S rRNA genes have been studied in a large number of organisms (reviewed in Korn 1982; Geiduscheck and Tocchini-Valentini 1988; Willis 1993). Compared with the lower eukaryotes, thorough knowledge of the 5S rRNA genes in mammals is scarce. The

Abstract: The spontaneous diabetic syndrome of the diabetes-prone Bioa. Breeding (BB) rat is caused by selective T-cell-dependent autoimT -1 mune destruction of the insulin-producing pancreatic 13 cells (Crisfi r~4HRI2) et al. 1992). A profound T-cell lymphopenia appears to be a preD4Mit6 requisite for the onset of the disease (Markholst et al. 1991a, 1993; Lyp Cris~i et al. 1992). Lymphopenia is inherited and can be attributed to a fully penetrant and recessive allele of the lymphopenia resisNF~4HRI1 ) m , tance gene (Lyp; Guberski et al. 1989; Markholst et al. 1991a). The n importance of examining Lyp to study the pathogenesis of insulindependent diabetes mellitus (IDDM) in BB rats is therefore obviand a cloning effort must build on accurate and precise poTtr~RI2)~..,, OUS, sitioning of the gene. Recently Lyp was mapped to the neuropepD4Mit5 tide Y (Npy) region on rat Chr 4 (RNO4) positioned 0.7 cM distal to D4Mit7 [being a simple sequence length polymorphism (SSLP) D4Mit6 marker from the flanking sequence of Npy; Jacob et al. 1992]. Lyp Later an erratum was published reporting this position to be faulty Npy because of interchanges of DNA samples and reporting a position (D4MitT) proximal to Npy (Jacob et al. 1994). However, this erratum defined n neither the precise location of Lyp nor the genetic distance from Npy. We therefore performed an SSLP analysis on a total of 854 backcross animals from three pedigrees in which lymphopenia was D4Mit6 segregating. Three different backcross pedigrees were used. F~ animals Lyp from crosses between Iyp/lyp diabetes-prone (DP)-BB/HRI and, N pYHRI1 ) ~ respectively, non-lymphopenic and diabetes-resistant (DR)-BB/ n HRI, Brown Norway (BN)/Mol, and New England Deaconess Hospital (NEDH)/Mol rats were backcrossed to DP-BB/HRI, producing 322, 348, and 184 backcross animals, respectively. Presence or absence of lymphopenia was determined with peripheral blood samples obtained just after weaning. Following immunolabeling with a F1TC-conjugated rat T-cell receptor, Tcr=~, specific antibody (clone R73, Serotec), the percentage of Tcr,~/3positive leukocytes was determined by flow cytometry (Markholst et al. 1991a). Lymphopenia was defined as <20% Tcr § leukocytes (mean + SD: 7.9 + 0.2%) and non-lymphopenia as >20% Tcr § leukocytes (mean + SD: 42.9 + 0.5%). No animals with Tcr + leukocytes between 17.9 and 24% were detected. All three pedigrees confirmed the expected 1:1 segregation of lymphopenia (Markholst et al. 1991a, 1991b, 1993). A total of 854 BC('~ ' ' x DP-BB/HRI) animals were analyzed using the polymerase chain reaction (PCR) primers of Jacob and associates for the microsatellites D4Mit5, -6, and -7 (the latter from Npy flanking sequence). An alternative primer set that amplifies another microsatellite (D4HRII) in an intron in the Npy gene (Larhammar et al. 1987; primers: 5 '-AGGGAGTGGCAGCATTTAGGG-3' and 5'-CAGAAGAAACCCATGGTTCGT-3') was used in the NEDH/Mol and DR-BB/HRI-derived pedigrees, since D4Mit7 did not show any polymorphism in these crosses. In addition, we used a SSLP (D4HRI2) found in the flanking sequence of the Trypsin-1 (Try-l) gene (Craik et al. 1984; primers:

Abstract: The critical role played by the RET protooncogene during development of the nervous and excretory systems and during the neoplastic transformation of a number of cell lineages of neural crest origin has been suggested by recent findings. Germline mutations, affecting different domains of the RET protooncogene, have been identified in Multiple Endocrine Neoplasia type 2A (MEN 2A; Donis-Keller et al. 1993; Mulligan et ai. 1993) and type 213 (MEN 2B; Carlson et al. 1994; Eng et al. 1994; Hofstra et al. 1994), in Hirschsprung disease (HSCR; Edery et al. 1994; Romeo et al. 1994), and in Familial Medullary Thyroid Carcinomas (FMTC; Donis-Keller et al. 1993; Mulligan et al. 1994). Somatic mutations of the RET gene were also found in a subset of sporadic Medullary Thyroid Carcinomas (MTC) (Blaugrund et al. 1994; Zedenius et al. 1994). In addition, a knock-out mouse model has shown, in the homozygous state, complete absence of intestinal ganglion cells and renal agenesis (Schuchardt et ai. 1994). Both the human and the mouse RET protooncogene have already been cloned (Takahashi et al. 1989; Iwamoto et al. 1993) and their chromosomal locations mapped. In particular, RET was assigned by fluorescent in situ hybridization (FISH) to human Chromosome (Chr) 10ql 1.2 (Ishizaka et ai. 1989), and by linkage analysis to mouse Chr 6 (Copeland et al. 1993). The rat counterpart of this gene has not been isolated so far. In order to facilitate studies in rat similar to those carried out in mouse and human on the RET protooncogene and to enrich the mouse-rat and human-rat homology maps, we have addressed the issue of isolating and mapping the rat RET protooncogene. Amplification of a rat DNA fragment homologous to part of the human and murine RET protooncogene was achieved by setting up a PCR reaction in a total volume of 50 gl containing 250 ng of rat genomic DNA, 50 pmoles of the appropriately designed degenerate primers RR1F (5\"-GACCAGSCNGCCGGCACNCC3') and RR2R (5\"-ACAGCCTGGCCANTGRCA-3'), 1.25 U of Taq polymerase, and 200 mM of each dNTP in a 10 mM Tris-HC1, 50 mM KC1, 1.5 mM MgCI 2 (pH 8.3) amplification buffer. Thirtyfive cycles of amplification were performed at 94~ for 1 rain, 65~ for 1 rain, and 72~ for 3 rain. A final elongation step at 72~ for 5 min was also carried out. The 1.9-kb DNA band observed after electrophoresis of the PCR product in a 0.8% low melting point agarose gel was of the size expected on the basis Of the distance between the two degenerate primers in the human gene (Ceccherini et al. 1993). The band was cut out and reamplifled under the same PCR conditions. A few microliters of the purified product of this latter PCR amplification were used for cloning the 1.9-kb rat genomic DNA in an appropriate plasmid vector (TA cloning kit, Invitrogen). Both strands of the clone TA(1

Abstract: References: 1. Rowe, L.B., Nadeau, J.H., Turner, R., Frankel, W.N., Letts, V.A., Eppig, J.T., Ko, M.S.H., Thurston, S.J., Birkenmeier, E.H. (1994). Mann . Genome 5, 253-274. 2. Bredt, D.S., Hwang, P.M., Glatt, C.E., Lowenstein, C., Reed, R.R., Snyder, S.H. (1991). Nature 351,714-718. 3. Kishimoto, J., Spun-, N., Liao, M., Lizhi, L., Emson, P., Xu, W. (1992). Genomics I4, 802-804. 4. Xn, W., Gomaan, P., Sheer, D., Bates, G., Kishimoto, J., Lizhi, L., Emson, P. (1993). Cytogenet. Cell Genet. 64, 62-63. 5. Lowenstein, C.J., Diner 9 J.L., Snyder, S.H. (1994). Ann. Intern. Med. 120, 227-237. 6. Huang, P.L., Dawson, T.M., Bredt, D.S., Snyder, S.H., Fishman, M.C. (1993). Cell 75, 1273-1286. 7. Kozak, C.A., Stephenson, D.A. (1993). Mamm. Genome 4 (Suppl.), $72-$87.

Abstract: Gonadotrophin-releasing hormone (GnRH) is released from the hypothalamus in discrete pulses and transported to the pituitary , gland in the hypothalamic-portal venous system. GnRH binds to the gonadotrophin-releasing hormone receptor (GNRHR) on cells in the pituitary gland to stimulate the synthesis and release of follicle-stimulating hormone (FSH) and hiteinizing hormone (LH). GnRH and GNRHR play key roles in the control of reproductive function in both males and females. GNRHR is a G-protein-coupled receptor with seven putative transmembrane domains and has been cloned from several species including human (Chi et al. 1993; Kakar et al. 1992) and sheep (Brooks et al. 1993). Recently, the GNRHR locus was mapped to human Chromosome (Chr) 4q 13.1-q21.1 (Kaiser et al. 1994). This region of human Chr 4q contains some genes whose ovine homolog are linked to the Booroola fecundity gene (FecB) that increases ovulation rate and litter size in sheep (Montgomery et al. 1993). GNRHR is a strong candidate for the site of the FecB mutation. Physiological studies with homozygous (BB), heterozygous 03+) and non-carriers (++) of the FecB mutation have shown that there are differences between genotypes in ovarian follicular development, concentrations of gonadotrophins in plasma, and pituitary responses to exogenous GnRH (McNatty et al. 1991a; Montgomery et al. 1992a). There were no differences between the genotypes in the hypothalamic content of GnRH (Gale et al. 1988) or in the patterns of secretion of GnRH (McNatty et al. 1993). However, differences between genotypes were observed in GnRH-induced FSH release in ewes following hypothalamic-pituitary disconnection (McNatty et al. 1991b) leading to the conclusion that at least part of the effect of the FecB mutation acts at the level of the pituitary gland to increase its responsiveness to physiological concentrations of GnRH. There were no gene-specific differences in the affinity of GnRH receptors in the pituitary gland, although differences were noted between the genotypes in the numbers of GnRH binding sites at different stages of the estrous cycle (Fleming et al. 1990). A \"gain of function\" mutation or a mutation that changed the turnover of GnRH receptors may explain the increased responsiveness of BB ewes to GnRH, leading to increased FSH concentrations and higher ovulation rates. The FecB locus maps to sheep Chr 6 between the genes for secreted phosphoprotein 1 (SPP1) and epidermal growth factor (EGF; Montgomery et al. 1993, 1994). This region shows extensive homology with human Chr 4q and with mouse Chrs 3 and 5. In the mouse, GNRHR maps close to platelet-derived growth factor receptor ot (PDGFRA) and Hardy-Zuckerman 4 feline viral oncogene homolog (KIT) on Chr 5 (Kaiser et al. 1994). PDGFRA and KIT are located on sheep Chr 6 some distance from the FecB

Abstract: Rob joined us at the outset, in November 1992. We enlisted his help as an Associate Editor because of his wide experience and phenomenal productivity in the field of chromosome evolution and animal, particularly vertebrate, cytogenetics. He has played a major role in the growth and development of Chromosome Research and I have specially appreciated his decisive and business-like manner in carrying out his editorial work for the Journal. I am sure the same would be said by the many groups of authors who have submitted their papers through his office.

Abstract: Tyrosine kinases are integral elements in the transduction of signals from the cell surface to the nucleus. Various receptorassociated cytoplasmic tyrosine kinases are involved in signaling events that accompany the binding of antigen and other extracellular signals by T and B lymphocyte surface receptors. The Src family of tyrosine kinases is comprised of 10 (or more) members (Src, Fyn, Lyn, Lck, Fgr, Hck, Yes, Blk, Frk, and Yrk; Lee et al., 1994; Bolen et al. 1992; Sudol et al. 1993). Most of these appear to be present as human and routine homologs and, with the possible exception of Frk, are expressed in various hematopoietic cells. The expression of some members appears to be modulated during development (Law et al. 1992). The general structure of Src family tyrosine kinases consists of an N-terminal \"gene-specific region\" of -200 amino acids, with a myristylation site at Gly 2, Src homology domains SH3 and SH2, and a conserved kinase domain 9 27 with a carboxy-terminal regulatory tyrosine residue (Tyr s ). Some of the Src kinases have been shown to be associated with transmembrane receptors such as Lck with the CD4/CD8 complex in T cells (Turner et al. 1990) and Fyn with the TCR, IL2 or B cell receptors (Samelson et al. 1990). Studies of these protein tyrosine kinases have provided important insights into the genetic regulation of T cell development and function. In addition, members of a smaller kinase family, Syk/Zap70 (Taniguchi et al. 1991; Chan et al. 1992) have been implicated in T and B cell antigen receptor signaling (Chen et al. 1994b). An autosomal recessive form of severe combined immunodeficiency results from mutation of the ZAP-70 gene in humans (Arpaia et al. 1994; Elder et al. 1994; Chan et al. 1994a). Members of a third protein tyrosine kinase family, Jak, also are implicated in cytokine receptor signaling (Darnell et al. 1994). A fourth family of kinases, the six Tec-related tyrosine kinases, have been identified: Tec (Mano et al. 1990), Drosophila Dsrc28C (Gregory et al. 1987), Btk (Vetrie et al. 1993; Tsukada et al. 1993), itk-tsk/Emt (Siliciano et al. 1992; Heyeck and Berg 1993; Gibson et al. 1993), Txk (Haire et al. 1994), and, most recently, Bmx (Tamagnone et al. 1994). These genes are classified as a separate family (subfamily) from the Src kinases. The Tec gene itself is a complex comprised of multiple expressed forms (Sat(} et al. 1994). Furthermore, Srm, a recently identified gene, possesses some features of both the Src and Tec families (Kohmura et al. 1994), suggesting that there may be kinases not fitting strictly within either family. Like Src gene products, the Tec kinases appear to be important in hematopoietic cell development (Heyeck and Berg 1993) and recognition-related signaling. EMT, the human homolog of itk/tsk, has been shown to be involved early in the B7/CD28 signal pathway in T lymphocytes (August et al. 1994).

Abstract: Involucrin is a precursor of the cornified envelope (CE), an insoluble layer of transglutaminase-crosslinked proteins that is assembled underneath the plasma membrane in the outer layers of the epidermis (Simon 1994). Involucrin is widely used as a marker of keratinocyte terminal differentiation, since it is expressed both in the epidermis and in keratinocyte cultures (Watt 1989). The mechanisms regulating involucrirl expression are of interest as a paradigm of gene expression during keratinocyte terminal differentiation. During evolution of primates from nonprimates, the gene for involucrin has undergone major alterations through changes in the short tandem repeats that constitute much of the coding region (Green and Djian 1992). The coding sequence of involucrin from at least 19 species has been determined, and in those species, including mouse, where the site of onset of involucrin expression has been examined, it is in the outer, differentiating epidermal layers (Djian et al. 1993; Green and Djian 1992). Although the evolution of the involucrin coding sequence has been the subject of extensive investigation, very little is known about the noncoding regions and only the human promoter has been characterized (Carroll and Taichman 1992; Carroll et al. 1993; Eckert and Green 1986; Takahashi and Iizuka 1993). The human involucrin gene has a relatively simple structure, consisting of a 5' untranslated exon of 43 bp and a second exon of 2107 bp bearing the uninterrupted coding region; the exons are separated by an intron of 1188 bp (Eckert and Green 1986). Some potential regulatory motifs have been found upstream of the TATA box, including a 'Blessing' motif, which is present in many other epidermally expressed genes (Blessing et al. 1987; Fuchs 1993), and two canonical AP-1 binding sites (Takahashi and Iizuka 1993; Fig. 1). The presence of these AP-1 sites (or TPA-responseelements) is of interest because involucrin expression is induced by TPA or transfection of c-jun and c-los (members of the AP-1 family of transcription factors) into keratinocytes (Takahashi and Iizuka 1993; Yaar et al. 1993). Although the intron is not required to direct expression of the involucrin promoter to the differentiating epidermal layers in transgenic mice (Carroll et al. 1993), in vitro transfection experiments suggest that the intron does have some regulatory activity (Carroll and Taichman 1992). In order to identify which of the potential regulatory elements found in the human involucrin gene have been conserved through evolution, we sequenced the equivalent region of the mouse gene (1303 bp) and aligned it to the human sequence. The deduced structure of the mouse gene is consistent with the size of the mRNA (1.5 kb, P. Djian, personal communication). The region

Abstract: 3. Cremers, F.P.M., Armstrong, S.A., Seabra, M.C., Brown, M.S., Goldstein, J.L. (1994). J. Biol. Chem. 269, 2111-2117. 4. Andres, D.A., Seabra, M.C., Brown, M.S., Armstrong, S.A., Smeland, T.E., Cremers, F.P.M., Goldstein, J.L. (1993). Cell 73, 1091-1099. 5. Cremers, F.P.M., van de Pol, D.J.R., van Kerkhoff, E.P.M., Wieringa, B., Ropers, H.H. (1990). Nature 347, 674--677. 6. Seldin, M.F. (1994). Mamm. Genome 5(Suppl.), S1-$21. 7. Green, M.C. (1988). Mouse News Lett 82: 111.

Abstract: To determine consistency in usage of pedigree symbols by genetics professionals, we reviewed pedigrees printed in 10 human genetic and medical journals and 24 medical genetics textbooks. We found no consistent symbolization for common situations such as pregnancy, spontaneous abortion, death, or test results. Inconsistency in pedigree design can create difficulties in the interpretation of family studies and detract from the pedigree's basic strength of simple and accurate communication of medical information. We recommend the development of standard pedigree symbols, and their incorporation into genetic publications, professional genetics training programs, pedigree software programs, and genetic board examinations.

Abstract: Species: Mouse Locus name: Cadherin-11 Locus symbol: cadll Map position: Acadm/DSmMtl l-(2.2)-cadl 1-(2.2)-Zfp4 Method of mapping: six different RI strains: AXB, BXA, AKXL, BXD, BXH, LXPL Database deposit information: EMBL databases accession number X77557 Molecular reagents: A 481-bp HindIII-fragment from the 3'untranslated region of the cadherin-ll (3170 bp-3651 bp) was used as a hybridization probe. Allele detection: RFLP analysis of a BglII polymorphism. The 4.7-kb band and the 7.2-kb band correspond to restriction fragment length variants of cadherin-ll gene (Fig. 1). Previously identified homologs: Human homolog is cadherin-11 [1] Discussion: Our data show that cadherin-11 is located on mouse Chromosome (Chr) 8 between Acadrn and Zfp4 (Fig. 2). In the same region two other cadherins, the E-cadherin (Urn) and P-cadherin (cadP), are localized [2]. These two cadherins were mapped by interspecific backcross analysis. For E-cadherin, 11 recombinants out of 75 were found between Urn and esterase-1 (Esl; 14 cM distal) and 1 recombinant out of 36 between Um and tyrosine amino-transferase (Tat; 5 cM proximal) [3]. Hatta and coworkers found no recombinants between P-cadherin, E-cadherin, and haptoglobin (Hp), also using interspecific backcross mapping [4]. In the BXD panel, 7 recombinants out of 26 between cadll and Esl were found, so cad11 maps distally to Esl similar to Urn. No information is currently available on the mapping of metallothionein-1 (Mtl) and adenine phosphoribosyl transferase (Aprt), which were used as flanking markers in the study of Hatta and associates [4]. On the basis of all the data available, it is c/ear that all three cadherins map distally from Esl. The M-cadherin gene (locus Cdh3) has also been mapped by interspecific backcross analysis using Urn and Tat as markers [5]. In this case, however, recombinants were found between Cdh3, Urn, and Tat, placing Cdh3 5 cM distally to Tat, and Tat 2.5 cM distally to Urn. In contrast to E-,Pand M-cadherin, the N-cadherin gene is not located on Chr 8 but maps to Chr 18 [6].