Genomics 57, 365–370 (1999)Article ID geno.1998.5205, available online at http://www.idealibrary.com on

A Radiation Hybrid Map of Mouse Chromosome 13

Rosemary W. Elliott,1 Kenneth F. Manly, and Colleen Hohman

Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, New York StateDepartment of Health, 666 Elm Street, Buffalo, New York 14263

Received September 15, 1997; accepted December 18, 1997

to generate a map that is used by many workers (Hud-A mouse radiation hybrid (RH) panel was used to son et al., 1995). A framework map of the whole human

make a framework map for the entire length of mouse genome has also been constructed using this panel (Gy-chromosome (Chr) 13. Forty-one loci were typed, and apay et al., 1996). An STS map of the human genomewhile most used primers flanking simple sequence re- was generated using the Stanford G3 panel of 83 hy-peats, some genes were included. The most proximal brids (Stewart et al., 1997).and distal loci are D13Mit132 and D13Mit35. The esti- A RH panel recently developed by Dr. Peter Goodfel-mate of map length for Chr 13 is 1328 cR. The map is low (Schmitt et al., 1996) is now available for thecompared with the same set of loci from the consensus mouse. Mouse cells were exposed to 3000 rads of Xmap for Chr 13, which is 70 cM in length, and also with irradiation and fused with the nonirradiated hamstera recombinational map derived from an intraspecies cell line A23. DNA was isolated from 100 cell hybrids.cross typed for many of the same loci. The mouse RH Recombinational maps are available for the mouse ge-panel gave good resolution for Chr 13 and at the distal

nome, and several interspecies maps now include manyend allowed separation of previously nonrecombinantloci (Rowe et al., 1994; Kozak et al., 1990; Copeland etmarkers that are present on a single 620-kb YAC clone.al., 1993). However, there are still many loci that, dueData analysis was performed using the RH option forto lack of genetic variation, cannot be typed on geneticMap Manager QT. This framework RH map of Chr 13maps. Furthermore, map order for markers typed onis the second of a series of RH maps for mouse chromo-different crosses is tentative. These problems can besomes. q 1999 Academic Press

remedied using radiation hybrids because all loci thathave been sequenced can be typed on RH panels, asthere is no requirement for genetic variation.INTRODUCTION

To begin to use RH maps to answer genetic ques-tions, it is necessary to generate framework maps forThe use of radiation hybrids (RHs) to generate long-all chromosomes. In this study we present a frameworkrange maps of chromosomes was an important step inmap of mouse chromosome (Chr) 13, using the Goodfel-human genetics. The map of human chromosome 21low hybrid panel (McCarthy et al., 1997). We also de-was the first example (Cox et al., 1990). This studyscribe a new computer program based on Map Manageralso included a statistical approach to measuring the(Manly, 1993) that will hold the typing data, generateproportion of breaks, u, between two loci, based on themap distances in centirays, calculate lod scores (Cox etnumber of hybrids containing DNA breaks between theal., 1990), and allow linkage of new markers to beloci. This statistic is modified by a mapping functiontested and established.that converts the distance to centiRays (cR). Finally,

the study provided a lod score function representingMATERIALS AND METHODSthe degree of support for linkage between two loci.

Since the initial studies, radiation maps have beenRadiation hybrids. A panel of DNA from 100 mouse–hamsterproduced for other single human chromosomes, such

RH clones was purchased from Research Genetics, Inc. DNA samplesas a map of human chromosome 11 with over 500 loci were arrayed in 96-well Falcon microtest plates. For each amplifica-(James et al., 1994) and human chromosomes X, 18, tion, 20 ng of DNA from each clone was transferred, using a multi-

channel pipette, to a second plate. PCR primers for loci defined by12p, and 9p (Bouzyk et al., 1996; Giacalone et al., 1996;amplification of markers described by MIT (Dietrich et al., 1994)Kumlien et al., 1996; Raeymaekers et al., 1995). Thewere obtained from Research Genetics. We thank Dr. Richard SwankGeneBridge Panel 4 (Walter et al., 1994) has been usedof the Roswell Park Cancer Institute (RPCI) for primers for Cf2r(coagulation factor 2 receptor) and Dhfr (dihydrofolate reductase).The primer pair for Mekk (MEK kinase) was found by searching the1 To whom correspondence should be addressed. Telephone:

(716) 845-3277. Fax: (716) 845-8169. E-mail: relliott@mcbio.med. Mouse Genome Database and was synthesized at the RPCI Biopoly-mer Facility.buffalo.edu.

365 0888-7543/99 $30.00Copyright q 1999 by Academic Press

All rights of reproduction in any form reserved.

AID GENO 5205 / 6r61h$$281 04-14-99 14:21:19 gnma

ELLIOTT, MANLY, AND HOHMAN366

PCR. PCR using the above primers was carried out in multiwell range and pattern of lengths of fragments are similarplates in the PTC-100-96 thermal cycler (M. J. Research, Inc.) in a to those found in a RH panel for human chromosome10-ml volume containing 20 ng of genomic DNA, 1 to 2.5 pmol of each

X (Kumlien et al., 1996). For instance, there are severalprimer and 0.08 unit of Taq polymerase. The mixture also containedcases in which both a long fragment and a short adja-0.05% bovine serum albumin, 1.5 mM MgCl2, 10 mM Tris–HCl, 50

mM KCl, and 1 ml 2% cresol red dye in 60% sucrose. The cycling cent fragment are present in the same hybrid, but theparameters used were 947C for 3 min, followed by 947C for 45 s, 557C intervening DNA appears to be absent. Data from suchfor 35 s, 727C for 30 s for 38 cycles, with the last extension time 5 min. hybrids were checked for errors both by rereading theAnalysis of the reaction product was performed by electrophoresis on

pictures and by retyping the samples.2% Seakem LE agarose gels (FMC Products) in 0.51 Tris-boratebuffer, pH 8.3. The apparatus was purchased from Owl Scientific. The map. The RH map for the loci used in Fig. 1 isThe wells were formed using three 42-slot multiwell combs, and 3 the central map in Fig. 2. The order of most loci wasml of each reaction mixture was loaded using a multichannel pipette.

previously known. Typing data for each locus wereElectrophoresis was carried out for 45–60 min at 200 V and frag-therefore placed in the predicted position in the dataments were visualized after ethidium bromide staining. Gels were

photographed on thermal paper K65HM (Mitsubishi) using the window. Locus order was tested by moving the dataAlpha Imager 2000 Digital Imaging System (Alpha Innotech Corp.). for a locus to a more proximal position and noting the

Retyping of questionable data was performed using AmpliTaq Gold change in the number of apparent breaks and in thepolymerase as suggested by the manufacturer. Use of this productlod score for linkage for markers affected by the change.caused a decreased signal for misprimed hamster fragments and

allowed us to type samples with greater confidence. The test was continued by moving the locus to a moreData analysis. Genetic data were stored in an enhanced version distal position and noting the changes in the same pa-

of Map Manager QTb15, available at http://mcbio.med.buffalo.edu/ rameters. The final position was chosen to minimizemmQT.html, which is itself an enhanced version of Map Manager the number of breaks and maximize the LOD for link-Classic (Manly, 1993). The enhanced version contains a radiation

age. For all of the 41 markers, the positions are basedhybrid analysis option. The typings were entered in a data windowon odds for linkage greater than 10,000:1.similar to the data window used to analyze genetic backcrosses. Map

distances and lod scores were calculated according to Cox et al., The RH map was compared to a map of many of the(1990). The program can store data, generate a map with distances same loci derived from the intraspecies backcross (ICR/in centirays, present a statistical analysis of data for each locus, Ha 1 C57BL/6Ha) 1 C57BL/6Ha [(IB)B] (Jacoby et al.,store comments, and generate haplotype figures. The distance and

1994) on the right of Fig. 2. This map uses data onlylod score are based on two-point analysis from adjacent markers.The ability to adjust the position of the markers expands the capacity from female F1 hybrids. The loci present in both mapsfor analysis. Genetic analyses were performed using this program, have the same order, except for the adjacent markerswhich was also used to draw the RH map shown in Fig. 2. Typing D13Mit1 and D13Mit216. A further comparison of theand retention data are available at http://www.jax.org/resources/doc

RH map was made with the same loci from the mostuments/cmdata/rhmap/rh.html.recent consensus map (Justice and Stephenson, 1996).This consensus map was constructed using all pub-RESULTSlished data for Chr 13. An initial map, based mainlyon multilocus backcrosses and the MIT F2 cross (Die-Choice of PCR primers. To develop the frameworktrich et al., 1994), was generated, and data frommap, loci defining SSRs (Dietrich et al., 1994) weresmaller crosses and RI strains were then incorporatedchosen to span the full length of Chr 13, including theusing interpolation. The order of markers from differ-most proximal and most distal loci. Preference wasent crosses is not as reliable as is the order of markersgiven to SSRs that had already been typed together infrom the same cross. On the left of Fig. 2 is a map ofthe backcross (ICR/Ha 1 B57BL/6Ha) 1 C57BL/6Hathe consensus positions of the loci typed on the RH map(IBB) and to those that identify genes.and there is generally good agreement between the twoTyping. DNA samples from the panel were ampli-maps. However, the locus order in the consensus mapfied using each set of primers, and the presence or ab-differs from the locus order in the RH map at the proxi-sence of specific amplification products was determinedmal end of Chr 13. The RH map shows that the mostafter agarose gel electrophoresis of the amplified prod-proximal locus is D13Mit132, and the backcross mapuct. Data were entered into Map Manager QT and ana-is consistent with this, but this locus is placed morelyzed using the RH option. The typings for 41 loci aredistally in the consensus map. The order of several ofshown in Fig. 1, which indicates which loci were ampli-the other proximal loci also differs from that found infied in each of the 100 hybrids. The assumption is madethe consensus map and in the map obtained from thethat if adjacent loci are retained in the same hybrid,MIT F2. In a more distal region, the consensus mapthen the intervening DNA is also retained. Under thisshows that Cf2r is proximal to Dhfr. In the RH map,assumption, Fig. 1 illustrates the lengths of DNA frag-Dhfr is proximal to Cf2r, consistent with recent recom-ments from Chr 13 retained within each RH. Thebinational data for this region (Seymour et al., 1996).lengths range from the full length of Chr 13 in RH lines

Fragment retention. The retention of loci is deter-56 and 79 to a single locus in nine RH lines. Elevenmined by the fraction of hybrid cells containing a givenhybrids appear to contain no DNA from mouse Chr 13,locus. Retention for Chr 13 loci in this RH panel isand 1 hybrid contains eight fragments. However, asshown in Fig. 3 and ranges from 19 to 44%, except formore loci are typed, short stretches of DNA from Chr

13 may be identified in some of these hybrids. The the most proximal marker, which is retained by 61%

AID GENO 5205 / 6r61h$$281 04-14-99 14:21:19 gnma

MOUSE CHR 13 RADIATION HYBRID MAP 367

FIG. 1. Cell lines showing presence of DNA for Chr 13 loci. Cell lines are numbered as received from the vendor and as listed in MapManager QT files. Loci are listed in map order, with the centromere at the top. A vertical line indicates the presence of specific mouseDNA, as demonstrated by its ability to be amplified with primers associated with the listed loci. Continuous lines indicate that there is noevidence of a break in DNA present in that line.

of the lines. This is consistent with high retention at except for the proximal 10 map units in the consensusmap and for two genes in the distal portion of Chr 13.centromeric loci found for human chromosomes. The

average retention for 41 loci is 29.5%. There are slight The order of loci defined by SSRs in the consensus mapis based largely on the map of the MIT F2 cross (Dietrichvariations along the chromosome, but no dramatic

changes. Retention for the distal loci ranges from 19 et al., 1994). A search of their database showed that sev-eral of the proximal markers were typed as dominantto 32%, while retention for the proximal half of the

chromosome appears higher, 25 to 40%, if the most markers, when one homozygote could be typed unequivo-cally, but the heterozygotes could not be distinguishedproximal locus is ignored. These values do not appear

to differ from retention estimates observed in human from the other homozygote. This means that these mark-ers were placed on the map with very low odds. The RHhybrid panels.map places these proximal loci with odds greater than100,000 to 1. Furthermore, the order for many of the lociDISCUSSIONis confirmed by the (IB)B backcross. Further confirmation

A radiation hybrid framework map of mouse Chr 13 comes from physical maps of the region generated duringwas generated. The map was obtained using a new the analysis of the beige mutation, now Lyst (Misumi etprogram to analyze RH data, the RH option for Map al., 1997; Perou et al., 1997). One of the crosses (MisumiManager QT. In this initial use of the program the et al., 1997) places D13Mit216 proximal to D13Mit1, inprobable order of the markers was known. The order agreement with the RH map, while the other placespredicted from the data was tested first by minimizing D13Mit1 proximal, in agreement with our results for thethe number of breaks and second by maximizing the genetic cross. Reversing the order of these two markers inlod scores for linkage between the loci. the RH map generates four more apparent chromosomal

The map obtained using these criteria was compared breaks.A difference between the RH map and the recombina-to the consensus map. The locus order was the same

AID GENO 5205 / 6r61h$$281 04-14-99 14:21:19 gnma

ELLIOTT, MANLY, AND HOHMAN368

FIG. 2. Maps of Chr 13. All maps are oriented with the centromere at the top. The center map was derived from the data presented inFig. 1, using calculations as described (Cox et al., 1990). Positions of loci are given in centirays. The map on the left was obtained from theconsensus map, using the distance from the centromere in centimorgans as the map position for each locus. The horizontal bars on thevertical line of the map represent 10-cM intervals. To illustrate order differences, proximal loci in these two maps are linked by dashedlines. On the right is a recombinational map for Chr 13, obtained from intraspecies cross (IB)B. Most loci in this cross were also typed onthe RH DNA. Map distances represent percentage of recombination obtained after assigning a position of 0 to the most proximal marker.

tional maps is that the relative distances for some in- number of factors could contribute, some from the datafor the RH map and some from the recombinationaltervals are altered. The fraction of the map length occu-

pied by the proximal 15 loci, to D13Mit116, is much data.If X-ray-induced chromosomal breaks occur ran-greater for the RH map (41%) than either in the consen-

sus map or for the same interval in the map generated domly, then the RH map should represent a physicalmap. However, if breaks are not random in some re-using the (IB)B cross (16.6%). Eliminating the proximal

locus, which has a high retention frequency, and using gions, this could affect relative distances. For Chr 13,the retention frequency appears slightly higher in thethe interval D13Mit216 to D13Mit116 gives 33.9 and

11.6% of the RH and recombinational maps, respec- proximal regions (Fig. 3) and this may be a contributingfactor. Errors in the typing of some loci could lengthentively. The basis for this difference is not clear, but a

AID GENO 5205 / 6r61h$$281 04-14-99 14:21:19 gnma

MOUSE CHR 13 RADIATION HYBRID MAP 369

breaks would increase the estimate of chromosomallength. Map length estimates are also affected by er-rors, which vary in their effects depending on whetherthe error is a false positive or a false negative. Errorsthat generate new breaks increase the apparent maplength, while errors that eliminate breaks decrease theapparent map length. In this study, all results thatwere not internally consistent were retested and inde-pendently assessed by two individuals.

FIG. 3. Retention frequency plot. The number of lines amplifying The mouse genome contains approximately 3000 Mbeach locus was obtained from Map Manager QT and is plotted against of DNA, so an average-sized chromosome like Chr 13the loci, which are presented in the same order as in Figs. 1 and 2. should contain about 150 Mb. In making the RH mapEach bar in the histogram is to the right of a number, which repre-

for Chr 13, we have identified 445 radiation-inducedsents the order of loci in Figs. 1 and 2.breaks in the 100 cell lines, which is a minimum esti-mate. On this map, 1 cR represents 113 kb, and the

the RH map by introducing spurious chromosomal average resolution of the map is 3.8 Mb per interval.breaks. To remove typing errors, we have retyped sev- No report of genetic recombination between the mosteral loci, particularly those that indicate the retention distal SSR markers, D13Mit77 and D13Mit35, has yetof short DNA fragments amplified by only a single lo- been made. These markers are on the same 620-kbcus, such as D13Mit132. On the other hand, with only YAC clone y60E7 (Yen et al., 1997), but are separated41 loci typed, not all the bins have been defined, so the in the RH panel by breaks in six hybrids. The RH mapmap length could increase as more loci are added and thus allows these two loci to be ordered relative tomore short pieces of DNA are identified, each with two neighboring loci and orients the map of YAC y60E7 tobreaks that would contribute additional map length. the chromosome. Two loci on the map, D13Rp3 and

We have previously reported compression of the dis- D13Rp4, are about 4 kb apart (Yen et al., 1997). Theretal end of the recombinational map of Chr 13 in the is one break between them, which does not order them(IB)B cross (Yen et al., 1997). This compression can be relative to the rest of the chromosome. These loci, asseen at the distal end of the recombinational map in well as D13Mit196, are on YAC y72G2. D13Mit53 mapsFig. 2. There is no recombination between D13Mit148 between these markers, but does not amplify YACand the loci distal to it, while the RH map shows that y72G2, suggesting that this YAC carries a deletion be-the region occupies 181 cR. There is also map compres- tween D13Rp4 and D13Mit196.sion on distal Chr 13 in crosses involving Mus spretus, Three of the loci, D13Mit161, 169, and Cf2r, havepossibly due to the presence of a ribosomal gene cluster, been used to obtain a physical map around pearl (pe)Rnr13 (Eicher and Shown, 1993). We have chosen to (R. Swank, unpublished). The order obtained from theuse the (IB)B cross in Fig. 2 because, unlike crosses RH map is the same as that obtained from the physicalinvolving M. spretus, there appeared to be no map com- map. Similarly, several of the loci have been used topression for proximal Chr 13 loci. Map compression can obtain a physical map of the region around beige (bg,be seen in the map obtained from (C57BL/6J1 SPRET/ now Lyst) (Barbosa et al., 1996, Misumi et al., 1997,Ei) 1 C57BL/6J (http://www.jax.org/resources/docu- Perou et al., 1997). The order for the physically mappedments/cmdata/maps/MapList.html), in which D13Mit1 loci is also the same as that found here for the RHand D13Mit3 are nonrecombinant, while they would be panel.about 8 map units apart in the (IB)B backcross mapand are 331 cR apart on the RH map. Map compression ACKNOWLEDGMENTSon proximal Chr 13 has also been observed in a cross

This work was supported by NIH Grant GM33160 to R.W.E., alsoinvolving male meiosis, C57BL/6Ha 1 (ICR/Ha 1by NCI Core Grant CA16056-21 to the RPCI. The development ofC57BL/6Ha), for the two strains used in the (IB)B crossMap Manager was partly supported by NIH Grant HG00330 to The(Elliott et al., 1997). Despite the recombination ob-Jackson Laboratory.

served at proximal Chr 13 in the (IB)B cross, it is possi-ble that some recombinational compression does exist

REFERENCESin this region, as suggested by the differences in frac-tional map length described above. Barbosa, M. D., Nguyen, Q. A., Tchernev, V. T., Ashley, J. A., Detter,

The length estimate of the map is 1328 cR. Map J. C., Blaydes, S. M., Brandt, S. J., Chotai, D., Hodgman, C., Solari,R. C., Lovett, M., and Kingsmore, S. F. (1996). Identification oflengths are dependent on the amount of radiation usedthe homologous beige and Chediak-Higashi syndrome genes. Na-to generate the hybrids. It is thus difficult to compareture 382: 262–265.map lengths between different hybrid sets. As some of

Bouzyk, M., Bryant, S. P., Schmitt, K., Goodfellow, P., Ekong, R.,the map intervals in Fig. 2 are quite long, it appears and Spurr, N. (1996). Construction of a radiation hybrid map oflikely that other breaks associated with short chromo- chromosome 9p. Genomics 34: 187–192.somal fragments or short deletions in long fragments Copeland, N. G., Jenkins, N. A., Gilbert, D. J., Eppig, J. T., Maltais,

L. J., Miller, J. C., Dietrich, W. F., Weaver, A., Lincoln, S. E.,may be present in some of these intervals. Finding such

AID GENO 5205 / 6r61h$$281 04-14-99 14:21:19 gnma

ELLIOTT, MANLY, AND HOHMAN370

Steen, R. G., Nadeau, J. H., and Lander, E. S. (1993). A genetic Kumlien, J., Grigoriev, A., Crollius, H. R., Ross, M., Goodfellow, P.,and Lehrach, H. (1996). A radiation hybrid map spanning the en-linkage map of the mouse: Current applications and future pros-

pects. Science 262: 57–66. tire human X chromosome integrating YACs, genes, and STSmarkers. Mamm. Genome 7: 758–766.Cox, D., Burmeister, M., Price, E., Kim, S., and Meyers, R. (1990).

Radiation hybrid mapping: A somatic cell genetic method for con- Manly, K. (1993). A Macintosh program for storage and analysis ofstructing high-resolution maps of mammalian chromosomes. Sci- experimental genetic mapping data. Mamm. Genome 4: 301–313.ence 250: 245–250. McCarthy, L. C., Terrett, J., Davis, M. E., Knights, C. J., Smith,

Dietrich, W. F., Miller, J. C., Steen, R. G., Merchant, M., Damron, A. L., Critcher, R., Schmitt, K., Hudson, J., Spurr, N. K., Goodfel-D., Nahf, R., Gross, A., Joyce, D. C., Wessel, M., Dredge, R. D., low, P. N. (1997). A first-generation whole genome-radiation hybridMarquis, A., Stein, L. D., Goodman, N., Page, D. C., and Lander, map spanning the mouse genome. Genome Res. 7: 1153–1161.E. S. (1994). A genetic map of the mouse with 4006 simple sequence Misumi, D. J., Nagle, D. L., McGrail, S., Dussault, Jr., B. J., Smutko,length polymorphisms. Nature Genet. 7: 220–245. [Supplemented J. S., Chen, H., Charlat, O., Duyk, G. M., Ebeling, C., Baldini, L.,by additional markers in Whitehead Institute/MIT Center for Ge- Carlson, G. A., and Moore, K. J. (1997). The physical and geneticnome Research, Genetic Map of the Mouse, Database Release 11 map surrounding the Lyst gene on mouse chromosome 13. Geno-(July 1995)]. mics 40: 147–150.

Eicher, E. M., and Shown, E. P. (1993). Molecular markers that de- Perou, C. M., Perchellet, A., Jago, T., Pryor, R., Kaplan, J., and Jus-fine the distal ends of mouse autosomes 4, 13, and 19 and the sex tice, M. (1997). Comparative mapping in the beige–satin region ofchromosomes. Mamm. Genome 4: 226–229. mouse chromosome 13. Genomics 39: 136–146.

Elliott, R. W., Manly, K. F., Hohman, C., Zhang, Y., Marshall, D. J., Raeymaekers, P., Van Zand, K., Jun, L., Hoglund, M., Cassiman, J-and Jacoby, R. F. (1997). Comparison of male and female maps of J., Van den Berghe, H., and Marynen, P. (1995). A radiation hybridmouse autosomes. Submitted for publication. map with 60 loci covering the entire short arm of chromosome 12.

Giacalone, J., Li, X., Lehrach, H., and Franke, U. (1996). High den- Genomics 29: 170–179.sity radiation hybrid map of human chromosome 18 and contig of Rowe, L. B., Nadeau, J. H., Turner, R., Frankel, W. N., Letts, V. A.,18p. Genomics 37: 9–18. Eppig, J. T., Ko, M. S., Thurston, S. J., and Birkenmeier, E. H.

Gyapay, G., Schmitt, K., et al. (1996). A radiation hybrid map of the (1994). Maps from two interspecific backcross DNA panels avail-human genome. Hum. Mol. Genet. 5: 339–346. able as a community genetic mapping resource. Mamm. Genome

5: 253–274.Hudson T. J., Stein, L. D., Gerety, S. S., Ma, J., Castle, A. B., Silva,J., Slonim, D. K., Baptista, R., Kruglyak, L., Xu, S. H., et al. (1995). Seymour, A. B., Yanak, B. L., O’Brien, E. P., Rusiniak, M. E., Novak,An STS-based map of the human genome. Science 270: 1945–1954. E. K., Pinto, L. H., Swank, R. T., and Gorin, M. B. (1996). An inte-

grated genetic map of the pearl locus of mouse chromosome 13.Jacoby, R. F., Hohman, C., Marshall, D. J., Frick, T. J., Schlack, S.,Genome Res. 6: 538–544.Broda, M., Smutko, J., and Elliott, R. W. (1994). Genetic analysis

of colon cancer susceptibility in mice. Genomics 22: 381–387. Stewart, E. A., McKusick, K. B., Aggarwal, A., Bajorek, E., Brady,S., Chu, A., Fang, N., Hadley, D., Harris, M., Hussain, S., Lee, R.,James, M. R., Richard, III, C. W., Schott, J-J., Yousry, C., Clark,Maratukulam, A., O’Connor, K., Perkins, S., Piercy, M., Qin, F.,K., Bell, J., Terwilliger, J. D., Hazan, J., Dubay, C., Vignal, A.,Reif, T., Sanders, C., She, X., Sun, W.-L., Tabar, P., Voyticky., S.,Agrapart, M., Imai, T., Nakamura, Y., Polymeropoulos, M., Weis-Cowles, S., Fan, J.-B., Mader, C., Quackenbush, J., Myers, R. M.,senbach, J., Cox, D., and Lathrop, G. M. (1994). A radiation hybridand Cox, D. R. (1997). An STS-based radiation hybrid map of themap of 506 STS markers spanning human chromosome 11. Naturehuman genome. Genome Res. 7: 422–433.Genet. 8: 70–76.

Walter, M., Spillett, D., Thomas, P., Weissenbach, J., and Goodfellow,Justice, M. J., and Stephenson, D. A. (1996). Mouse chromosome 13.P. (1994). A method for constructing radiation hybrid maps ofMamm. Genome 6: S232–S244. [Supplemented by information inwhole genomes. Nature Genet. 7: 22–28.http://www.informatics.jax.org/bin/ccr/current/contents?13]

Kozak, C. A., Peyser, M., Krall, M., Mariano, T. M., Kumar, C. S., Yen, C.-H., Pazik, J., Zhang, Y., and Elliott, R. W. (1997). An intersti-tial telomere array proximal to the distal telomere of mouse chro-Pestka, S., and Mock, B. A. (1990). Molecular genetic markers

spanning mouse chromosome 10. Genomics 8: 519–524. mosome 13. Mamm. Genome 8: 411–417.

AID GENO 5205 / 6r61h$$281 04-14-99 14:21:19 gnma