Mammalian Genome 3: $274-$288, 1992

: enome 9 Springer-VerlagNew York Inc. 1992

Mouse X Chromosome Stephen D.M. Brown, 1'* Phil Avner, 2 and Gail E. Herman 3 1Department of Biochemistry and Molecular Genetics, St. Mary's Hospital Medical School, London W2 1PG, UK; 2Unite de Genetique Moleculaire Murine, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, Cedex 15, France; 3Institute for Molecular Genetics, One Baylor Plaza, $911, Houston, Texas 77030, USA Received February 19, 1992

Introduction

The genetic and physical map of the mouse X Chromosome (Chr) has continued to grow since the first X Chr report (Brown et al. 1991). Nearly 120 loci have now been assigned to the DNA probe map of the mouse X Chr (Fig. 1), and there has been a concomitant expansion in regions that have been physically mapped. This report introduces a number of new features, some of which reflect the growing physical map.

New features All the known mutations mapping to the mouse X Chr are now included in the locus list (Table 1). Full details of the phenotypic effects for most of these mutations can be found in the latest edition of Genetic Variants (Lyon and Searle 1989). As was indicated in the previous report, insufficient information is available to subsume accurately the bulk of mutations on the mouse X Chr into the detailed probe map. We have continued to indicate the map positions of these mutations alongside the probe map (Fig. 1). Most of these mutations have been mapped relative to either the Ta or Pip (jp) loci, both of which are incorporated on the probe map. The mutant map and the probe map have been aligned accordingly. However, this year we have indicated the standard errors of map position for each mutation (details from Lyon and Searle 1989), and this allows the reader to make an improved judgment of the likely position of any mutation on the probe map. With a growing emphasis on the detailed physical mapping of the mouse X Chr and the construction of the first mouse X Chr YAC clone contigs, we have presented a separate figure summarizing the available

physical map data (Fig. 2). Outline physical maps are presented that illustrate intergenic distances and show the positions and extent of overlying YAC clones. A number of YACs have been isolated from the screening of several mouse YAC clone libraries with various mouse X Chr probes. It is likely that this collection of mouse X Chr YACs will burgeon rapidly and require cataloguing. For this reason, we have introduced in this report a first listing of YAC clones from the mouse X Chr which indicates both their origin and the known loci that each clone covers (Table 2). We have continued to update a listing of somatic cell hybrids (Table 3). It is also important to note that there is no change to the established reference loci for the mouse X Chr. These are indicated on the probe map in Fig. 1. For further details readers are directed to the previous report (Brown et al. 1991). A large number of comments need to be addressed concerning the revision of the mouse X Chr map. As in the first report, comments will be considered in a number of sections which represent the major conserved linkage groups between mouse and human X Chr.

Centromere

The locus Gf-1, encoding a transcription factor, maps close to the centromere in the mouse and shows no recombinants with Cybb (Chapman et al. 1991b). In human, the homologous GFI has been shown to map at Xpl 1.23 and well separated from CYBB at Xp21.1.

Cybb-DXS674h, position 1-11 Reference loci: Otc Human conserved linkage group: Xp21.1-Xpll.22

Committee members: Y. Boyd, V.M. Chapman, C. Faust, R.M.J.

Hamvas, and S. Rastan *Chair of Committee for Mouse X Chromosome

A number of new conserved genomic clones from the short arm of the human X Chr have been mapped to

S.D.M. Brown et al.: Mouse X Chr

CEN sf Td

t

8. F" t A1/2 T37H TTm7 T T13RIL A2 A2/3

$275

)

DXWasTO

I

~ b

-

p,o

,

Of- 1

I, DXF34h-t I

- - DXPas7 (=DXS32h) H DXS676It A2 (DXPasg) 1 Obelx H Maoa, Maob m fSyn-I ,Ttmp I ~fL - - Ar~ 1 DXPas3.XIr-I, [DXSmh141,

A3

A4 l( A5/6

1

D

I

DXSmhI72

DXWas68 ,DXSmh15 ]

~

HDXPe,s5 H DXSmhlO, DXSmh222HLamp2HDX-S674h

A-D(Syp) -

A62~

O~3h

-

l

~

1

Xlr-2 HDXSmh219 DXSI44h (= DXPas6)

1

H Hq (DXSrah19I, DXSrah66, DXSmh67)

~

Mcf-2 1

Bn

~ ~ t

7.5~

dose to Bn

(DXSmh36, DXSmh59, DXSmh91)

HD~255

Fu~-I, DXS296h

lds - - lGabra-3 , DXBayl O

Str

A7/B

i

B~

1

~

m, E I ~

f8A D ~ 5 2 h (-DXPasS), D ~ I

~DXBay2, DXBay6 (=DXPa52Q DXS2S4Eh.]DXS253Eh. IG6pd,_~_:8- ] 7, DXPasI 3, 1 1 2 ~ q (= mdx) DXSmh DXSmh9, DXPasI4, DXSmh23, DXSmh64 - - Bmp4 1 DXSaff't120 1 I [ Pola. DXCrcI40, DXCl"c28, --

Pfffr

TI6H D

sla

T~2-~1 Xce

I l]

I

[DXCrc131, ~ ( = ~ m )

1

DX~c169], Ta

--

Bhd

~-1

I[Ccg-l, 1g~

Sit-

DX~I71

mo 1

Ym

DXCrc177, DXC~318 , X i s t ] HMimd

-- ~

D

--

]]DXPos19

--

DXCrcl I2, DXC~323 H DXPas23 DXSmh44, DXCrc47 DXCrc98H DXPas2

--

DXP~24 H Odc-13

4~ ~d

3

TI4RI I D/EFI - - DPCWasl7 17 DXPas25

F1 Fig.

1. L e g e n d

i

Aea

--

DXPastO

on facing page.

the proximal region of the mouse X Chr (Laval and Boyd 1992). Two of these markers, DXS676h (Xp21.1p l l . 4 ) and DXS674h (Xpll.22), confirm and extend the major conserved linkage group in this region from CYBB (Xp21.1) to ARAF (Xp11.4-pll.23). The mapping of DXS674h indicates that the observed con-

served linkage group in this region appears to extend over some 11 cM from the Cybb locus to the DXS674h locus. However, Gf-1, which on the human X appears to map distal to DXS674h at X p l l . 2 2 , might be expected to map within this linkage group and just proximal to DXS674h on the mouse X. As discussed above,

55F1 -

~ ~ DXPas20 (= DXSIOlh), Scar, DXMIT3 - - DAPasl5 (= DXS178h) 17 DXSmt~25 17 DXMIT4 I

Xca t

- - Prpst

T6R1

- - Co14~5, Alos21I DXSmh43

F3

-

DXPasl 17IHyp

65

-FZ rl m DXPasI8 [1 Cbx-rsl

F3

-- Prps2 Gy Li

(DXMITS) (Glra-2)

F3]F4 (Pdha-l)

Xpl (DXCzv181) ~-DXYMovI5

Crm Pal"

=__ =. =_ =._

=._ =._

-- Sts =.

Sxr

Fig. 1. Probe map of the mouse X Chr. (1) Genetic map. The principal aim of the map is to indicate accurately the established order of DNA probes derived in general from multipoint crosses, but also in a few instances from physical mapping studies. This is clearly most critical for markers that are genetically closely-linked: (i) where order is given, closely linked markers have been tested in the same cross and order derived from haplotype information; (ii) markers that have been analyzed in the s a m e cross and fail to show recombinants (and thus no order is available from haplotype information) are indicated on the same line separated by commas; (iii) markers that by inference from genetic data appear to map to the same location but that have n o t b e e n t e s t e d f o r l i n k a g e r e l a t i o n s h i p s in the s a m e cross and for which no order can be inferred are separated on the same line by a double slash (II); (iv) markers that have been tested in m o r e t h a n o n e cross are indicated in bold type and are joined to the map by a bolder line; because of their wider use they might be considered as molecular anchors when comparing data from different crosses; (v) markers that have been only loosely localized, or about which there is some inconsistency in the data concerning their location, are indicated in parentheses 0 and are disembodied from the map, though their approximate position is indicated; (vi) r e f e r e n c e loci are indicated by heavy boxes; and (vii) three loci for which no DNA probes are available have been in

cluded in the m a p - - H q , B p a , H y p , and T a - - a s they have all been included in multipoint analyses. They form useful reference points with the classical genetic map (see below). (2) Chromosomal location. (i) Markers that have been l o c a l i z e d b y in situ h y b r i d i z a t i o n on the G-banded map of the X Chr are underlined and the band location indicated. (3) Physical mapping. (i) Groups of markers for which there is p h y s i c a l linkage are bound by square brackets []. (4) Relationship of probe map to genetic map. The approximate position of a number of genetic loci for which no DNA probe is available is also indicated on an adjacent map. Because their position with respect to the detailed probe map is unreliable, they are not subsumed within the probe map itself. For the bulk of these loci in the central span of the chromosome, their genetic relationship has been determined relatively accurately with respect to the Ta locus (included on the probe map), and the two maps have been aligned accordingly. More distal probes have often been mapped with respect to thejp (=Pip) locus, and again the maps have been aligned accordingly at this point. Bars define the standard errors of map position for each mutation (Lyon and Searle 1989). The alignment of these two maps should allow the identification of DNA probes that are likely to lie in the vicinity of any genetic locus, though no information on order can be assumed.

S.D.M. Brown et al.: Mouse X Chr

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Table 1. Locus list for mouse X Chr. Locus Ag$ *A/as2

Amg Ar(=Tfm) Araf

Bhd Bmp4a Bn

Bpa Cbx-rsl *Cdr Ce&.I Cf.8 Cf-9 *Co14A5 Crm Cybb Dmd

C~nr namc T Alpha galaetosidase B,D Aminolevulinate B,D synthetase Amelogenin B,D Androgen receptor B,D,V v-mr encogenr B,D homolog 1 Broad-headed V Bone morphogenetic protein 4 (prev.Bmp 2b2) D Bent-tail V Bare patches V Chromobox related D Cerebellas degeneration related protein B,D Cell cycle, G1 B,D phase defect Coagulation factor B,D VIIIC Coagulation factor IX B,D Collagen a5 type IV B,D Cream V Cytochrome b-245 B,D Dystmphin B,D,V

Method I,L L

Band F1

L S,L,Dy S,L L S,L L L L L L, P

a/_as2

Xpll-Xq12

AMG AR ARAF1

Xp22.31-Xp22.1 Xql 1.2-Xql2 Xp11.3-Xp11.23

Reference 42, 62, 83 V. Chapman, ud 29, 65, 69 17,37,53,66,81 3,6,55

CDR COG1

Xq27.1-Xq27.2 Xq13.1

77 39, P. Avner, V. Chapman, G. Herman, ud 77 60, 62 57, 65 71 24, 35, 97

H. s~imbol H. location GLA Xq21.3-Xq22

CDPX2?

I,R,L,P

B

FSC

Xq28

3, 14,25,42,47,62, 83,91

I,L L L L I,L

A6

F9 COL4A5

Xq26.3-Xq27.1 Xq22

CYBB DMO

Xp21.1 Xp21.3-Xp21.1

3, 4, 42, 62, 83, 84 V. Chapman, ud 77 13, 84, 91 11,12,25,26,42,59,62,79,91,93

C

(=~) *DXBayl

DNA segment, Baylor College of Medicine

*DXBay2

D D D D D D D D DNA segment, Baylor, conserved from human D DNA segment, D Clinical Res. Centre

*DXBay3

*DXBay4 *DXBay5 *DXBay6 *DXBay7 *DXBay8 *DXBay9 *DXBayIO DXCrc13 DXCrc28 ,.~XCrc47 *DXCrc57 *DXCrc94 DXCrc98 DXCrc112 DXCrclM DXCrcI40 DXCrc169 DXCrc171 DXCrc177 *DXCrcI81 DXCrc187 DXCrclgO *DXCre202 DXCrc318 DXCrc323 *DXF34h-rsl *DXMITI *DXM IT3 *DXMIT4 *DXMIT5 DXNds3 (sedffimd) DXP as l

DXPas2 DXPas3 DXP as4 DXPas5 DXP as6 DXPas7 DXP aw8 DXPaw9 DXPa.~IO

(same as DXCm28)

D

S,L

61

S,LY S,L S,L

S,L SJj' S,L S,L S,L L,P S,L

Xqy8

sLY S,L S,L2 S,L SL SJ. SLY SLY SLY SLY S,L2

S. Kenwrlck, C. Faust, G. Herman, ud 15, 17, 18,66

R. Hamvas, S. Brown, ud

Xq12-Xq13

S S,L S,L SJ, SLY

56 R. Hamvas, S. Brown, ud 100 J. Keer, ud P. Cooper, ud

P. Cooper, ud

sL DNA segment, conserved from human DNA mierosatellite, MIT

L L,P

DXF34

Xp11.22-Xcen

Retroviral enhancer DNA segment, Pasteur Ir~timte

I,L

F3

I,L I,L

D/E A3 A4 A5/6

I,L I,L

I,L L

74, 99 G. Herman, ud 2, 38 3,91 7

DXS144E DXS32 DXS52

L L L,P A2

72 W. Dietrich, ud Faust and Herman, ud (DXMIT1)

Xq26.2 Xp22-Xp 11 Xq28

4,60,91 47, 62 6 6 Continued on next page

$278

S.D.M. Brown et al.: M o u s e X C h r

Table 1. Continued. I~$

Gcnc nasnr

DXPaal3 DXPaaI4 DXPasI5 DXPasI8 DXPasI9 DXPas20 DXPas21 DXPar22 DXPaw23 DXPas24 DXPas25 DXS253Eh (prey.P3) DXS254Eh (prev.Gdx) *DXS296h

see Dmd see Dmd

*DXS674h *DXS676h DXSmh7 DXSmh9 DXSmhl 0 DXSmh15 DXSmh23 DXSmh36 DX Smhr 3 DXSmM4 DXSmh59 DXSmh64 DXSmh66 DX Smh6 7 DX Smh91 DXSmhI20 DXSmh141 DXSmh172 DXSmh191 DX Smh219 DXSmh222 DXSmh225 DXSmh255 DXWasI 7 DXWas31 DXWas68 DXWas70 *DXWaM07 *DXYMovI5 *F8a *Fmr-I

c,@a Gabra-3

6f4 Gjb-1

(~rev. Corm32) Glra.2 Gs

~y nt,n Hq *Hyp le *Iris

see Rsvp

T D D D D D D D D D D D D

Band C C

H. s)rmbol H. location

DXSI78

Xq21.33-Xq22

DXSI01

Xq22

DXS253E

Xq28

3

I,L,P,S

DXS254E

Xq28

4, 11, 12, 14, 25.49, 91

D

nXS296

XqZV.3-Xq28

71

D D

DXS674 DXS676

Xpl 1.22-Xp1L21 Xp21.1-Xp11.3

72

24

24

79 79 12,25,50,66

D L,P L L L L L L L L L

86

A3

65 17, 66

D,L

DNA segment, Univ. of Washington

Mov pmviral flanking sequence Transcribed sequence in human F8 intron 22 Fragile X mental retardation - 1 Glucose-6-phosphate dehydroganase GABAA receptor a3 suburtit Erythroid transcription factor Gap junction membrane channd proteinbeta 1 Glyeinr receptor a2 subunlt Greasy Gyro Hypoxanthine phoaphoribosyl transferase Harlequin Hyphosphatcrnic rickets Eye-ear reduction Iduronate sulfatase

Referanr 59 59

L L L L L L L L L I,L,P,S

D DNA segment, conserved from human Harwdl, conserved from human see Dmd see Dmd DNA segment, St. Mary's Hospital

Method

I,L LL

L,P L L L L L L

A3

81 84, 86 84

IJ,

FI

41,42

I,L I,L,P I,L

F3 A3 A1 A3

I,L L

86 43 V. Chapman, ud

D

L,P

F8A

Xq28

B,D

L

FMR-I

Xq27.3

73 C. Faust and G. Herman, ud 48,71

B,D

L,P

G6PD

Xq28

14,90

B,D

L,P

GABRA3

Xq28

22, 38, 47, 62

B,D

L

GEl

Xp11.23

30

B,D

L

GJB1

Xp11.22-Xq 13

92 P. Avner, ud

B,D

L

GLRA2

Xp22.1-Xp21.3

38

HYP? HPRT

Xp22.2-Xp22,1 Xq26.1

77 77 2, 3, 27, 62, 63, 76, 91, 93

V L V L B ,D ,V I,S,L

A6

V V

L L

HYP?

Xp22.2-Xp22-1

12 65

V B,D

L L

IDS

Xq27.3-Xq28

77 48 Continued on next page

S.D.M. Brown et al.: Mouse X Chr

$279

Table 1. Continued. Locus It Llcam

T V

Method

Band

H. symbol H. location

833

I,L,P

AT/B

LICAM

Xq28

Reference 77 28,44,47,62

B,D

L

LAMe2

Xq24

V. Chapman, ud

V

L

/..,/

Getle name Irregular teeth L1 neural adhesion molecule Lysosomal membrane glyeoprotein 2 Lined

Maoa

Monoamine oxidase A

B,D

L

MAOA

Xpl IA-Xp 11.3

36, 70

Maob

Monoamine oxidase B

B,D

L

MAOB

Xp11.4-Xpl 1.3

36, 70

Mcf-2

mcf.2 trangforming sequr Viral integration site at retrovixal enhancer, also called DXNds3 Mottled Omithine decarboxylase pseudogene- 13 Ornithine transcarbamylase Octamer transcription factor 3h Patchy fur Pyruvate dehydrogenase E l a subunit Properdin factor, complement Phosphoglycerate kinase 1 Phosph~'ylase kinase eon~ollmg locus Phosphorylase kinase, alpha subunit Proteo~pid protein DNA polymerase alpha Rat phoaphof.bosyl pyrophosphate syn~helz.se 1 Rat phosphoribosyl pyrophosphate synthetase 2 Palate-tail-digit abnormalities Ribo6emal protein $4, gene on X Red sensitive visual pigment see Rps4 Scurfy Sex-linked anemia Sex-linked fidget Striated Steroid sulfatase Sex reversed Synapsin I Synaptophysin Tabby Tattered Trembly-like

B,D

I,L

MCF2

Xq26.3-Xq27.1

48, 54, 74

D

L

V D

L L

*Lamp2

Mintd

lifo Ode-13 Otc( =spJ) O~-3h

Pal Pdha.1 Pfc P gk-1

Phk Phka

Plp(=jp) Pola *Prpsl

*Prps2

ptd Rps4 Rsvp Scar sf s/a Sg SoSis Sxr Syn-1 Syp Ta Td Tgl(also

B,D,V I,L

77

A6/7

99 Seldin, M. and Taketo, M., ud

A 1/2

MNKZ

Xq13.2-Xql 3.3

77 45, 94, 96

OTC

Xp21.1

3, 62, 75, 83, 84, 101

D

L

V B,D

L I,L

F3/4

PDHA1

Xp22.1

67 19, 20

B,D

I,L

A2/3

PFC

Xp11.3-Xpll.23

46, 70

B,D

I,L

D

PGKI

Xq13.3

3,25,42,62,66,87,91

B

L

B,D

L,D

B,D,V L B,D I,P B,D L

95

77

D

PHKA

Xq 13.1

8, 17,24

PLP POLA

Xq21.33-Xq22 Xp22. l-Xp21.3

3, 32, 38 1 R. Hamvas, ud V. Chapman, ud

B,D

L

V

L

B ,D

L,P,S

RPS4X

Xql2-Xql3

51,58, 103

B ,D

L,P,R

RCP

Xq28

3,47,62,83,91

D V V V V

L L L L L

WAS? ASB?

Xpl 1.3-Xpl 1.22 Xp11.21-Xq21.31

IP2 ?

Xq27-Xq28

B

L

V B,D B,D V V V

L I,L S,D L,D L L

SYNI SYP EDA? IPI?

Xp11.23 Xpl 1.23-Xp11.22 Xql2-Xql3.1 Xpll.21-Xeen

B,D

L

TIMP

Xpl 1.3-Xpl 1.23

70, 83, 84

V B,D

L I,S,L

UBEI

Xp 11.23

77 43, 64, 82

V V

L L

NHSZ XIC?

Xp22.3-Xp21.2 XqI3

77 24

V

L

D

S,L.P

AGMXI? XIST

Xq21.33-Xq22 Xq13.2

D

L

77 10, 16, 58 52, g4

V. Chapman, ud

A2/3 A-D

102 P. Avner, ud 77, 78 77 77 77 77 77 3,84 88 2, 11, 12, 17, 18,66 77 98

D0 Timp

ty Ubel~

Xcat Xce

x/d *Xist Xlr-I

Tissue inhibitor of metalloproteinascs Trembly Ubiquitin-aedvating eazyme El (alsocalled Sbx, Als9x) X-linked cataract X-chromosomal controllingelem~mt X-linked immune deficiency Xi-apeeific tran~n'ipt X-llnked lymphocyte regulated gane 1

A2

Continued on next page

S . D . M . B r o w n et al.: M o u s e X C h r

$280 Table 1. Continued. Locus Xlr-2 Xpl Yrn Z,/x

Gene name X-linked lymphocyte regulated gene X-linked polydaetyly Yellow mottled Zinc f'mg~ protein, X-linked

T D V V B,D

Method L L L I,S,D,L,P

Band

H. symbol H. location

D

ZFX

Asterisks preceding loci denote a new locus added to last year's list. In the " H . symbol" column, potentially homologous human and mouse phenotypic mutants for which the gene(s) has not been cloned are listed with a question mark (?). In some instances, the evidence for homology is extremely strong; in other cases, it is much more speculative. For the Bmp4a gene, an X-specific band is detected in M. spretus, but not M. domesticus/musculus, suggesting the locus is a species-specific pseudogene. In the " T " column, D = DNA

Xp22.1

Reference 52, 84 77 77 8, 10, 16, 17,58,66,81,85,89

(any locus defined by a DNA sequence or clone); B = biochemical/protein/ immunological; and V = visible/other phenotype. In the " M e t h o d " column, I = in situ hybridization; S = somatic cell genetics; R = RI strains; L = linkage analysis by backcross or intercross; C = cytogenetic analysis (translocations, visible deletions, etc.); D = deletion analysis (molecular); H = radiation hybrid analysis; and P = physical mapping (PFGE, YACs, etc.).

Table 2. YAC clones from the mouse X Chr. ~s

Refea'~aee

Loci in YAC

Size (kb)

Librarya

Refea'nace

DXBay2

D19H6

DXBay2

180

P

G. Herman, ud

DXCrc57

SMH57

DXCrc57,DXCrcl40

500

Smh

R. Hamvas and S. Brown, ud

DXCrel40 DXCrc140

SMH57

DXCrc57,DXCrcI40 DXCRCI40, Pola

500

Smh

R. Hamvas and S. Brown, ud

SMt/140

700

Leh

R. Hamvas and S. Brown, ud

DXCrc318

SMH318

DXCre318, Xist

350

Smh

N. Brockdorff, ud

DXPas8

I)351:)6

P

G. Herman, ud

C39D5

DXPa~ DXPas8

270

DXPas8

300

P

G. Herman, ud

DXPasI9 DXPasl9

PA-1

DXPaM9, Xist DXPaM9, Xist

500

Lda

P. Avner, ud

PA-2

460

Leh

P. Avnor, ud

DXSmh141 DXSmh141 DXSmhI41 DXSmh141 DXSmh141 DXSrah141 DXSmh141 DXSrah141 DXSmh141 DXSmh141 DXSmh141 DXSmh141 DXSmh141 DXSmh141 DXSmh141 DXSrah141 DXSmh141 DXSrah141 DXSmhI41 DXSmh141

52(23 55D7 4gG11 18G13 5F5 50B5 34A4 17A7 64A5 64133 59H10 98A11 63A1 61H7 7gc10 68F2 71A10 96A7 94G5 26F4

DXSmh141 DXSmh141 DXSmh141 DXSmh141 DXSmh141 DXSrah141 DXSmh141 DXSrah141 DXSrah141 DXSmh141 DXSmh141 DXSmhI41 DXSmhI41 DXSmh141 DXSrah141 DXSmh141 DXSrah141 DXSmh141 DXSrah141 DXSmh141

190 450 240 430 290 290 280 220 200 310 350 210 350 500 260 300 240 550 390 360

Smh Smh Smh Smh Smh Smh Smh Smh Smh Smh Smh Smh Smh Smh Smh Smh Smh Smh Smh Smh

P. Mile.ham and S. Brown, ad

Fga

C131B2

F8a, DXMIT1

130

P

G. Herman, ud

Pola

SMH140

Pola, DXCrcI40

700

Leh

R. Hamvas and S. Brown, ud

Xist Xist Xist Xist

SMH318 PA-1 PA-2 PA-3

Xist, DXCrc318 Xist, DXPasI9 Xist, DXPasl9 Xist

350 500 460 3,300

Smh Leh Leh Leh

N. Broekdorff, ud P. Avner, ad P. Avner, lad P. Avner, ud

Zfx Zfx

SMH3 SMH9

Zfx Zfx

450 200

Leh Smh

R. Hamvas and S. Brown, ud R. Hamvas and S. Brown, ud

a Library origin of YAC clones: Leh: ICRF, C 3 H male partial RI library in AB1380 host (Larin et al. 1991). P: Princeton, C57 BL/6 female partial R1 library in ABI380 yeast host (Burke et al. 1991). Smh: St. Mary's, C57BL/10 female partial R1 library in rad52 recombination-deficient yeast host.

S.D.M.

Brown

et al.: Mouse

$281

X Chr

Table 3. Somatic cell hybrids. "X" only and derivative lines Name HYBX Clone 8

Mouse parout CAK 1D

Other patent T6120B1 (CHO) MA65 (Human)

Other Chrs

VI-6 VI-6 Thioguanine

Normal mouse s p l ~ Normal mouse

380-6 Cl-IO) 380-6 CLIO)

Rearr,mged 16 Rearranged 1.6 no X Derived frtxm VI-6

Refermeedsourc~ Disteeh* ea al. 1982 I. Craig, tmpubi.~lied data ; ,~'aar r M. 1985 Cox and Epstein 1985 P, Avner, un!:sublished data

Translouation X hybrids Name R6

Mouse pareaat T6R1

(X:7)

Other parent CH

Other C'hrs Un

CYT X F1

X breakpoint Plp+DXPasl-

N15 Ell** B20c12 IMSe I5d2" I5d3" G13N23 G13n28 R5B9DI

T6RI T14R1 T16H T16H T13R1 T13R1 TTR1 T7R1 T5RI

(X:7) (X:2) 0s (X:16) 0(:12) (X:12) (X:4) ~X:4) (X:7)

C C C C C C C C C

Y+Un Un No Y+Un No Y+Un No Y+Un No Y+Un No Y+Un No Y+Un Un

X F1 XF XD XD XA3 XA3 XA2 XA2 X F1

PIp+DXPas'~DXPas2+AgsDmd+ZfxDmd+ZfxOtc-M2e-raf+Cdr+St516-L11 + Otc-M2e-raf+Cdr+St516-L11 + Otc-M2c+ Otc-M2c+ Distal to DXPas18

Spe9

T3R1

(X:7)

CH

Un

XA2

?

H H H H H H H H H

Refere~aeeg'source T. Glaser, D. Housman, P. LMley unpublished data Avner et ~1. 19870 Avner et al. 1987b Avner et al. 1987b Avner et aL 1987b Avner et al. 1987"o Avner et al. 1987"o Avner et al. 1987b Avner et al. 198To T. G1aser, D. Housman, P, Lalley, P. Avner,unpublished data T. Glaser, D. Housman, P. Lalley, unpubfished data

** Possible deletion of terminal f r a g m e n t - - C h r 2 m a r k e r s missing. * Carries a secondary interstitial deletion. X deletion hybrids Name O3A P3K O3C O4A Q4C O4B S4A S1A O3H EBS4

Mouse parent ES cell line I-1I)3 ES cell line HD3 ES cell line HD3 ES cell lhae HD3 ES cell line HD3 ES cell line HD3 ES cell line HD3 ES cell line HD3 ES call line HD3 ?

O~er parent CH CH CH CH CH CH CH CH CH CH

Clone 8.111 Clone 8.1./2

1D ID

MA65 MA65

Other Chrs NT NT NT NT NT NT NT NT NT 13, 15, 17

X breakpoint Hprt+Zfx+Ar- .... Hprt+DXS253Eh+Zfx+Ar+L1 ] +Pgk+Plp-.... Hprt+Cdr+Fmr-I+VK21-.... Hprt+Cdr+Fmr-1-.... Hprt+Cdr+Fmr-l-.... Hprt+DXPas6+Cdr-.... Hprt+DXPas6-.... Hprt+DXS253Eh++Zfx.. Hprt+DXS253Eh++Zfx..... DXPas3-DXPas4-DXPas5-Hprt+ .... Otc-DXPas 3 Hp~+P3+Zfx-DXPas2-DXPas 1Ote-DXPas3 Hprt+P3+Zfx-DXP~2-DXPasl-

Rd'emace/sotn~c P. Avner, anpublished P. Av'ne~, unpublished P. Avner, unpublished P. Avner, unpublished P. Avner, unpublished P. Avner, unpublished P. Avner, unpublished P. Avner, unpublished P. Avner, unpublished Amar et al. 1985 ; Minna et aL1975 Herman et aL 1991 a Herman et al. t99ia

data data data

data data data data data data

.... indicates that the other loci tested distally are retained o r lost in accordance with the marker immediately to the left.

it appears to map close to Cybb. Mouse homologs of the repeat element in human DXF34h-rsl ( X p l l . 2 2 - cen) map close to the Otc locus (Laval and Boyd 1992). The mouse homolog of LAMP2 (Xq24) has been mapped at position 12, 6 cM proximal to Hprt (V. Chapman, unpublished data) and close to DXS674h. It would seem likely that Lamp2 maps distal to DXS674h and that Lamp2 forms one of the most proximal markers of the next conserved linkage group from Hprt to

Cf-8 (see below). A mouse homolog of the human UBE1 gene (Xpll.23) has been mapped into this conserved linkage group (Disteche el al. 1992; Kay et al. 1991a; Mitchell et al. 1991). A Y homolog has been identified and may encode a gene involved with spermatogenesis--Sby (Disteche et al. I992; Kay et al. 1991a; Mitchell et al. 1991). The scurfy mutant (sy3 maps proximal to Otc and shows many phenotypic similarities to Wiskott-Aldrich syndrome (WAS) in human (Lyon et al. 1990), which has now been shown to map between the TIMP (Xpl 1.3-pl i .23) and DXS255 (Xpl 1.22) loci on the human X Chr (Davies et al. 1992).

Hprt-Cf.8, position 18-30 Reference loci: Hprt and DXS253Eh Human conserved linkage group: Xq26-Xq28 A number of new genes have been mapped into the interval between Cf-9 and Gabra-3 including Cdr (Cerebellar degeneration-related protein), Ids (Iduronate sulfatase), and Fmr-1, the homolog of a human gene containing an unstable sequence involved in the Fragile X syndrome. A new microsatellite DXMIT1 (W. Dietrich, unpublished data) maps close to Bpa (G. Herman, unpublished data). In addition, extensive physical mapping has linked loci from Gabra-3 to Cf-8 (Faust and Herman 1991 and unpublished data) with intergenic distances established in detail for loci from DXPas8 to G6pd (Fig. 2). The detailed physical maps constructed in the region of the G6pd loci agree well with those originally reported by Brockdorff and colleagues (1989). The order of markers across this region is Gabra-3-F8a-DXPas8-CamL1-Rsvp-DXS254Eh-

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S.D.M. Brown et al.: Mouse X Chr

Table 3. Continued. Mouse X Oar irradiation hybrids 11.

Locus/probe

Hybrid 1 5 6 8 9 t0 12 13 15 19 2O 21 22 23 25 32 36 44 58 68 74 102 103 105 107 110 111 112 113 114 117 122 123 124 125 129 130 13I 133 134 137 138 139 140 141 142 143 145 146 148 149 150 151 t52 155

['-'g'-]

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.

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7

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§

4"

4"

+

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4"

+1

.

+

+

4"

4"

]

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4"

I

-

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VT-1 ;]

-r-~

4"] 4"]

I

7

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14" 4" *._t_l

-

~

4"

i

4"

4"

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+

+

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+

I

-

r

+

4"

+

+

I+1

+1

I§

+1

+ + + +

4"

+1

-14"

4"

I+1

4"7

m

+1

[-~+[

4" +

[+

r

+

14-i4"

+ +

r-~-

r-~

r-~

7

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4+

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+

+1

~._

E"

. ~[-'7-']

4"] 4"1

7

r-~

B

r-~

4"

r-~

% Retention

30

0

8

3

17

Distanc~from Ccnmxncrc

0

7

9

12

17

* Sefton et al. 1992.

7

50

6

0

11

2

6

6

8

5

5

6

2

6

5

5

2

29

31

34

36

38

38

40

43

44

44

46

50

56

67

72

22

S . D . M . B r o w n et al.: M o u s e X C h r

$283

Table 3. Continued. Mouse X Chr irradiation hybrids I*

Loeus/p~be

Hybrid A2 A3 BI

D2 D3 E1 E3 H2 I1 J2 K2 M3 N3 02 P1 P3 Q2

4"

+

+

4`

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4.

4`

4.

,

§

+

4"

4.

4"

4"

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4"

4"

4"

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+

+ I

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+

4"

4"

4"

I

"

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4.

4"

4"

4"

I +

ND

I

4"

4"

4"

4"

4"

+

4.

4"

4"

4"1 -

§

I+ 4"

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+

+

4"

4"

4"

4"

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J

4"14"

4"

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4"

4"

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ND § -

4"

4"

4.

4.

4"

4"

4"

4"

I 4"

4.

4"

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r-in

$2 T2 T3 U1 Vl V3 X2 Z1 Z2 AA1 AA2 AA3

4.

+

14"

4.1

4"

I

4"

4.T-

4"

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ND

4"

R1

4"

4"

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4"1

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4"

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4"

4.

4"

4"

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4.

4"

4"

Nq)

[§

§

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+

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22

4.1-

4"

I

CC3

DD1 DD2 EEl FF1 FF2 GG1

4"

4"

[ 4"

4.

4"

4"

4"

4"

4"

4"1

+

]

4"

4"

[-~

-

14"

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-eq_

+

% Retention

30

11

11

11

31

Distance from Ccntromere

0

7

9

12

17

26

1 4.] 4"

+

+t-

9

18

9

18

16

14

17

10

5

19

29

34

36

43

44

44

50

56

67

72

* Sefton et al. 1992.

DXS253Eh-G6pd-Cf-8. Order across the Gabra3 to Cf-8 region is conserved with the consensus gene order on the human X Chr as determined from physical mapping (Davies et al. 1992) aside from FSa, which in human is found within the F8C gene (mouse homolog, Cf-8) in human. The DXPas8 to L1Cam region is covered by a YAC clone contig (C. Faust and G. Herman, unpublished data; see Table 2). One YAC at the proximal end of this contig contains both the FSa gene and the microsatellite DXMIT1 and appears to indicate a locus order of DXMIT1-F8a-DXPas8 (G. Herman, unpublished data). A series of probes have been isolated by inter-repeat PCR (DXBayl-9) of the humanmouse hybrid 8.1/1 containing a reduced portion of the mouse X Chr (Table 3) extending from Hprt to DXS253Eh (Herman et al. 1991a). DXBay2 and DXBay6 map close to CamL1 (Fig. 2). DXBaylO, an

anonymous sequence conserved between mouse and human, maps close to Gabra3 (Fig. 1).

Dmd-Zfx, p o s i t i o n

31-34

Reference loci: Zfx Human conserved linkage group: Xp21.1-Xp22.1 Pulsed-field mapping studies have provided a detailed physical map encompassing the Pola, Zfx, DXCrcl40, and DXCrc57 loci (R.M.J. H a m v a s and S.D.M. Brown, unpublished data, and see Fig. 2). The physical map spans 1.5 Mb, and the order of loci is PolaDXCrc140-DXCrc57-Zfx. The region is covered by a YAC clone contig (details of clones in Table 2). The

$284

S . D . M . B r o w n et al.: M o u s e X C h r

................... D35D6 ....... - . c'3'B2, t .....................

A

C39D,

Gabra3

DXs,,,Io II )llll [llnllllltllll

FSa

DXPas8

V

V

iiiiiii tllll ilU iii iiii iiii ii iiiii

I

DXS254Eh

T " D19H6

..........

Rsvp

DX~ay2

y I

I

i

#, I

up to L 7Mb

I

$253Eh Cf-g

rV

I

I

I

IIIIIIIIIIIIIlllllllllllllllll n illllllllllll

up to 1Mb

c,6pa

CaroL1 Z.~.~._fx5'

B Pola I

I

pDP1068 BSXB2 Ks11

DXCrc140 DXCrc57

V

i

tv i

i

tVVt

t

i

i

SMH140'

C Gjb- 1

Ccg- 1

DXCrc171

•••••••••••••••••••••••••••••••••••

Phka ~

Rps4 I

I

DXCrc318

DXCrc177 [

[

I

I

I

I

I

up to 1Mb

,

I

Xist I

V

1............[

........

I

....

Xist

D t

r

i

t

i

i

t 'g i

DXPas l 9

i

'gt

................................

',,llllt...........

chimaenc

.............

i

i

PA-2

PA-3

Fig. 2. Physical maps of the mouse X Chr. Intergenic distances and overlying YAC clones from three areas of the mouse X Chr are indicated. Ruler interval = 100 kb. For a full discussion see text. (A) Physical mapping of the Gabra3-Cf-8 interval (G. Herman and C. Faust, unpublished data). (B) Physical mapping of the Pola-Zfx cluster (R. Hamvas and S. Brown, unpublished data). BSXB2 is a

g e n o m i c c l o n e l o c a t e d Y to the Z f x g e n e ; pDP1068 is a m o u s e au-

orientation of this cluster on the mouse X Chr has not been determined directly. However, on the human X Chr POLA maps between DMD and ZFX (Davies et al. 1992), indicating that the likely orientation on the mouse X Chr is cen-Pola-DXCrc140-DXCrc57-Zfxtel. The orientation of the Zfx gene on this map has been shown to be cen-3'-5'-tel (R. Hamvas, unpublished data). In the previous report, it was noted that DXCrc131 was physically linked to Ar with an intergenic distance of 1 Mb (Brown et al. 1991) and that Ar had been pulsed-field linked to DXCrc169, though intergenic distances were not well defined. However, experiments to link the Ar cluster with the Pola-Zfx cluster have been unsuccessful (R.M.J. Hamvas, unpublished data).

conserved linkage group in this region. Col4a5 maps distal to Plp as does the Prpsl gene (V. Chapman, unpublished data), whose human homolog maps to Xq21-q27. Three further microsatellites (DXMIT3-5) have been mapped to this linkage group (W. Dietrich, unpublished data). DXMIT3 cosegregates with Plp; the genetic relationship of the other two microsatellites with respect to the Probe Map is as yet poorly defined. The mouse Xist gene has been mapped just proximal to Pgk-1 (Borsani et al. 1991; Brockdorff et al. 1991a), and the map position of Rps4 has been further refined in this region (Hamvas et al. 1992b). Extensive pulsed-field analysis has been carried out across the Ccg-1 to Xist region (P. Cooper, unpublished data; J.T. Keer, unpublished data). Detailed pulsed-field maps (see Fig. 2) have been constructed in the vicinity of the Xist locus (P. Cooper, unpublished data) and indicate a gene order of cen-Phka-DXCrc177DXCrc318-Xist-tel. In addition, this area has been linked by pulsed field to more proximal loci including Gjb-I, Ccg-1, DXCrc171, and Rps4 (J. Keer, unpublished data). Moreover, Xist has been linked to the

Ar-CoMaS, position 36--62 Reference loci: Pgk-1 and Plp Human conserved linkage group: Xqt2-Xq22 The mapping of the Cot4a5 gene, which in human maps to Xq22, has better delineated the extent of the

tosomal 2.1 kb fragmentfromthe m o u s e Zfa gene (Keer et al. 1990) that detectsZfx codingand 3' sequences;KslI is a genomicclone5' to the Zfx gene. (C) Physicalmappingof the Phka-Xist cluster (P. Cooper, J. Keer, unpublished data). (D) Physical mapping of the Xist-DXPas19 interval (P. Avner, unpublisheddata).

S.D.M. Brown et al.: Mouse X Chr

distal marker DXPast9 by pulsed field and YAC cloning (P. Avner, unpublished data and see Fig. 2 and Table 2). Analysis of a new and large panel of irradiation hybrids of the mouse X Chr (Sefton et al. 1992) indicates that Gjb-1 maps proximal to Ccg-1. Overall locus order in this region is: cen-Gjb-l-Ccg-1-

DXCrc171-Rp s4-Phka-DX Crc177-DXCrc318-Xisttel. However, the intergenic distances of loci proximal to Phka are not yet well established. Where it has been determined, the gene order across the homologous region in human, A R - C C G 1 - R P S 4 X - P H K A - X I S T PGK1, is conserved with mouse (Davies et al. 1991). In addition, as expected, the conserved linking clone, DXCrc169, detects a homologous sequence close to EDA in Xql2-ql3 (Thomas et al. 1991). Finally, new mapping studies appear to have resolved the position of the DXNds3 locus, a microsatellite identified at a retroviral enhancer locus and originally mapped to position 26 proximal to Rsvp (Love et al. 1990). Independent mapping experiments with the probe Mintd derived from the enhancer locus indicated a more distal map location at position 42 (Fig. 1). However, further mapping experiments on DXNds3 in an interspecific backcross panel (G. Herman, unpublished data) place DXNds3 distal to Dmd and appear to indicate that DXNds3 and Mintd represent the same locus at position 42.

Hyp-Amg, position 65-72 Reference loci: DXWas31 and Amg Human conserved linkage group: Xp22.2-Xpter The mapping of the Hyp mutation has extended the limits of the most distal conserved linkage group on the mouse X Chr (Kay et al. 1991b). Hyp maps 7 cM proximal of Amg. In human HYP has been localised to Xp22.2-p22.1 and AMG to Xp22.3-p22.1. Hyp also maps 2 cM proximal to Cbx-rsl. Cbx-rsl represents a mouse homolog of a candidate mouse heterochromatin protein gene, M31, isolated by its homology to the Drosophila heterochromatin protein gene HP1 (Hamvas et al. 1992a). The Cbx-rsl locus has been shown to map between DXPasl and Amg (Hamvas et al. 1992a). However, three further autosomal loci appear to be detected by the M31 probe. In addition, Prps2 (localized at Xp22.3-p22.2 in human) appears to map into the Hyp-Amg interval. DXCrcl81, a conserved linking clone, maps to human distal Xp (N. Brockdorff, unpublished data) and would be expected to map into this interval. Finally, DXYMovI5, representing flanking sequence to a proviral insertion into the mouse pseudoautosomal region, has been shown to map only 0.5 cM distal to Amg (V. Chapman, unpublished data). This localizes the pseudoautosomal boundary and indicates that the total genetic map length of the mouse X Chr is 72 cM.

$285

2.

3.

4.

5.

6.

7. 8.

9. 10.

11.

12.

13.

14.

15. 16.

17.

References 1. Adler, D.A., Tseng, B.Y., Wang, T.S.-F., and Disteche, C.M.: Physical mapping of the genes for three components of the

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