Meiosis in male PL/J mice: a genetic model for gametic aneuploidy

Sperm from mice of the PL/J strain have a high frequency of sperm-head morphology abnormalities. Fluorescence in situ hybridization (FISH) methods revealed that PL/J sperm are also characterized by a high frequency of aneuploidy. The traits of abnormal sperm head morphology and aneuploidy are associated with numerous meiotic abnormalities. Spermatocytes of PL/J mice exhibit chromosome asynapsis during meiotic prophase as well as reduced crossing over, revealed by analysis of both MLH1 foci in pachytene spermatocytes and chiasmata seen at the first meiotic metaphase. During the first meiotic division, roughly one-third of the PL/J spermatocytes exhibit aberrant spindle morphology, with abnormalities including monopolar spindles, split spindle poles, and incomplete spindle formation and centrosomal abnormalities. F1 progeny of a cross between PL/J and C57BL/6J did not exhibit a high frequency of either sperm aneuploidy or sperm head morphology aberrations, as would be expected if the PL/J traits were dominant. Among progeny of a backcross of F1 mice to PL/J, none of 16 males assessed exhibited elevated frequencies of sperm head morphology abnormalities. Four of the individuals exhibited elevated sperm aneuploidy, but not at the levels of the PL/J parents. Thus, it is likely that the aberrant PL/J traits are due to several genes and/or modifiers affecting the generation of both sperm aneuploidy and abnormal sperm head morphology.     

Female expression of the H-2-linked sex-limited protein (Slp) due to non-H-2 genes

Female mice of 15 inbred strains in which males express the H-2-linked sex-limited protein (Slp) were tested for the production of this protein. Four inbred strains (FM, LG/J, NZB, PL/J) were found in which females produce Slp in the absence of hormonal manipulation. Crosses have been made between strains FM, NZB, or PL/J and several Slp-negative strains. Slp-typing of the F₁, F₂, and backcross progeny, as well as of a number of recombinant inbred strains, indicates that production of Slp by normal females of these strains depends upon the concurrent presence of an Slp-positive,H-t2-linked allele and of permissive alleles of one or two non-H-2 autosomal genes. Complementation studies with two of the strains (FM and PL) indicate that an identical genetic mechanism mediates expression of Slp in females of these two strains. FM-derived animals carrying the testicular feminization mutation (tfm) also express Slp, as do castrated NZB mice, indicating that Slp expression in these instances is not dependent upon testosterone as it is in other inbred strains. It is concluded from these results that genes distinct from the putative structural gene for Slp influence the sex-limitation of its expression.     

Ultrastructural differentiation of sperm tail region in Diplometopon zarudnyi (an amphisbaenian reptile)

Diplometopon zarudnyi, a worm lizard belongs to amphisbaenia under trogonophidae family. This species exists in limited areas of the Arabian Peninsula and is an oscillating digger found in sub-surface soils. The present study aimed to investigate the sperm tail differentiation in D. zarudnyi. Ten male adults of D. zarudnyi were collected from Riyadh during April–May 2011. To study the sperm tail at the ultrastructural level the testes were fixed in 3% glutaraldehyde, than post fixed in 1% osmium tetaroxide followed by dehydration in ethanol grades; samples were cleared in propylene oxide and embedded in resin. Tail formation begins by the moving of centrioles and mitochondria towards the posterior pole of sperm head. Simultaneously many microtubules of the midpiece axoneme were enclosed by a thick layer of granular material. Mitochondria of midpiece lie alongside the proximal centriole which forms a very short neck region and possess tubular cristae internally and concentric layers of cristae superficially. During this course a fibrous sheath surrounds the axoneme of mid and principal piece. At the end dissolution of longitudinal manchette takes place. The mitochondria then rearrange themselves around the proximal and distal centrioles to form a neck region. Later, the fibrous sheath surrounds the proximal portion of the flagella. This part along with sperm head of D. zarudnyi provides a classical model that could be used in future for evolutionary and phylogenetic purposes of class reptilia.     

A linkage map of mouse Chromosome 1 using an interspecific cross segregating for the gld autoimmunity mutation

An interspecific backross was used to define a high resolution linkage map of mouse Chromosome (Chr) 1 and to analyze the segregation of the generalized lymphoproliferative disease (gld) mutation. Mice homozygous for gld have multiple features of autoimmune disease. Analysis of up to 428 progeny from the backcross [(C3H/HeJ-gld x Mus spretus)F₁ x C3H/HeJ-gld] established a map that spans 77.6 cM and includes 56 markers distributed over 34 ordered genetic loci. The gld mutation was mapped to a less than 1 cM segment on distal mouse Chr 1 using 357 gld phenotype-positive backcross mice. A second backcross, between the laboratory strains C57BL/6J and SWR/J, was examined to compare recombination frequency between selected markers on mouse Chr 1. Significant differences in crossover frequency were demonstrated between the interspecific backcross and the inbred laboratory cross for the entire interval studied. Sex difference in meiotic crossover frequency was also significant in the laboratory mouse cross. Two linkage groups known to be conserved between segments of mouse Chr 1 and the long arm of human Chrs 1 and 2 where further defined and a new conserved linkage group was identified that includes markers of distal mouse Chr 1 and human Chr 1, bands q32 to q42.     

An interstitial telomere array proximal to the distal telomere of mouse chromosome 13

Lambda clones of mouse DNA from BALB/c and C57BL/10, each containing an array of telomere hexamers, were localized by FISH to a region close to the telomere of Chr 13. Amplification of mouse genomic DNA with primers flanking SSRs within the cloned DNA showed several alleles, which were used to type eight sets of RI strains. The two lambda clones contained allelic versions of the interstitial telomere array, Tel-rs4, which is 495 bp in C57BL/10 and which includes a variety of sequence changes from the consensus telomere hexamer. Comparison of the segregation of the amplification products of the SSRs with the segregation of other loci in an interspecies backcross (C57BL/6JEi × SPRET/Ei) F₁× SPRET/Ei shows recombination suppression, possibly associated with ribosomal DNA sequences present on distal Chr 13 in Mus spretus, when compared with recombination in an interstrain backcross, (C57BL/6J × DBA/J) F₁× C57BL/6J, and with the MIT F₂ intercross. Analysis of recombination in females using a second interstrain backcross, (ICR/Ha × C57BL/6Ha) F₁× C57BL/6Ha, also indicates recombination suppression when compared with recombination in males of the same strains, using backcross C57BL/6Ha × (ICR/Ha × C57BL/6Ha) F₁. Thus, more than one cause may contribute to recombination suppression in this region. The combined order of the loci typed was D13Mit37–D13Mit30–D13Mit148–(D13Rp1, 2, 3, 4, Tel-rs4)–D13Mit53–D13Mit196–D13Mit77–(D13Mit78, 35). Data from crosses where apparently normal frequencies of recombination occur suggest that the telomere array is about 6 map units proximal to the most distal loci on Chr 13. This distance is consistent with evidence from markers identified in two YAC clones obtained from the region. Received: 24 September 1996/Accepted: 20 January 1997     

Mapping of the azh locus to mouse chromosome 4.

The azh (abnormal spermatozoon headshape) mutation in the mouse, which results in abnormal sperm head formation, was demonstrated to display an autosomal recessive pattern of inheritance. The azh locus was mapped by crossing mice with the mutation on a relatively pure C57BL/6J(B6) background with C3H/HeKam and backcrossing the F1 mice to B6-azh/azh mice. Up to 60 backcross progeny were typed for azh, by microscopic examination of sperm heads, and for other markers. Eleven loci on chromosomes other than 4 showed no significant linkage with azh. Glucose 6-phosphate dehydrogenase-1 (Gpd-1), located on the distal part of chromosome 4, showed 26% recombination frequency with azh, indicating significant linkage (P less than .001). Linkage with an anonymous DNA probe for the D4Rp1 locus in the central region of chromosome 4 was then analyzed, and only a 5% recombination frequency was observed. The map location indicates that azh is distinct from other known mutations that also result in abnormal sperm heads.     

Fine mapping of Ath6, a quantitative trait locus for atherosclerosis in mice

Ath6 is a novel quantitative trait locus associated with differences in susceptibility to atherosclerosis between C57BL/6J (B6) and C57BLKS/J (BKS) inbred mouse strains. Combining data from an intercross and a backcross (1593 meioses) between mice from B6 and BKS strains and from The Jackson Laboratory interspecific backcross panels, (C57BL/6J ×Mus spretus) F₁× C57BL/6J and (C57BL/6J × SPRET/Ei) F₁× SPRET/Ei, we constructed a consensus genetic map and narrowed Ath6 to a 1.07 ± 0.26 cM interval between the anonymous DNA marker D12Pgn4 and the gene Nmyc1. This region is near the proximal end of murine Chromosome (Chr) 12, which is homologous to the human chromosomal region 2p24-p25. Marker order in the Ath6 region was concordant among the two crosses and The Jackson Laboratory interspecific backcross panels. This high resolution map rules out candidate genes encoding apolipoprotein B, syndecan 1, and Adam17. The two Ath6 crosses have a combined potential resolution of 0.06 cM. Received: 12 September 2000 / Accepted: 22 February 2001     

Association of a sperm-specific protein with the mitochondrial F1F0-ATPase in Heliothis: Implications for sterility of H. virescens × H. subflexa backcross hybrids

Evidence is presented that a mitochondrial protein that displays a species-specific net charge in the Heliothis spp complex is associated with subunits of the F₁-ATPase. The expression of this 63 kd polypeptide, p63, was restricted to sperm and its developmental pattern of synthesis and accumulation paralleled that of the putative β-subunit of the F₁-ATPase complex. Comparisons of the enzyme from fertile Heliothis virescens and sterile (H. virescens × H. subflexa) backcross hybrid males revealed two differences. First, the specific activity of the F₁-ATPase isolated from sterile males was half that of preparations from fertile males; and second, the p63 protein was bound less tightly to the complex in backcross sperm. The implications of these findings in relation to both the identification of the cause of backcross male sterility and prospects for future research are discussed.     

Additive transgene expression and genetic introgression in multiple green-fluorescent protein transgenic crop × weed hybrid generations

The level of transgene expression in crop × weed hybrids and the degree to which crop-specific genes are integrated into hybrid populations are important factors in assessing the potential ecological and agricultural risks of gene flow associated with genetic engineering. The average transgene zygosity and genetic structure of transgenic hybrid populations change with the progression of generations, and the green fluorescent protein (GFP) transgene is an ideal marker to quantify transgene expression in advancing populations. The homozygous T₁ single-locus insert GFP/Bacillus thuringiensis (Bt) transgenic canola (Brassica napus, cv Westar) with two copies of the transgene fluoresced twice as much as hemizygous individuals with only one copy of the transgene. These data indicate that the expression of the GFP gene was additive, and fluorescence could be used to determine zygosity status. Several hybrid generations (BC₁F₁, BC₂F₁) were produced by backcrossing various GFP/Bt transgenic canola (B. napus, cv Westar) and birdseed rape (Brassica rapa) hybrid generations onto B. rapa. Intercrossed generations (BC₂F₂ Bulk) were generated by crossing BC₂F₁ individuals in the presence of a pollinating insect (Musca domestica L.). The ploidy of plants in the BC₂F₂ Bulk hybrid generation was identical to the weedy parental species, B. rapa. AFLP analysis was used to quantify the degree of B. napus introgression into multiple backcross hybrid generations with B. rapa. The F₁ hybrid generations contained 95–97% of the B. napus-specific AFLP markers, and each successive backcross generation demonstrated a reduction of markers resulting in the 15–29% presence in the BC₂F₂ Bulk population. Average fluorescence of each successive hybrid generation was analyzed, and homozygous canola lines and hybrid populations that contained individuals homozygous for GFP (BC₂F₂ Bulk) demonstrated significantly higher fluorescence than hemizygous hybrid generations (F₁, BC₁F₁ and BC₂F₁). These data demonstrate that the formation of homozygous individuals within hybrid populations increases the average level of transgene expression as generations progress. This phenomenon must be considered in the development of risk-management strategies.Communicated by J. Dvorak     

A major QTL for resistance to Gibberella stalk rot in maize

Fusarium graminearum Schwabe, the conidial form of Gibberella zeae, is the causal fungal pathogen responsible for Gibberella stalk rot of maize. Using a BC₁F₁ backcross mapping population derived from a cross between ‘1145’ (donor parent, completely resistant) and ‘Y331’ (recurrent parent, highly susceptible), two quantitative trait loci (QTLs), qRfg1 and qRfg2, conferring resistance to Gibberella stalk rot have been detected. The major QTL qRfg1 was further confirmed in the double haploid, F₂, BC₂F₁, and BC₃F₁ populations. Within a qRfg1 confidence interval, single/low-copy bacterial artificial chromosome sequences, anchored expressed sequence tags, and insertion/deletion polymorphisms, were exploited to develop 59 markers to saturate the qRfg1 region. A step by step narrowing-down strategy was adopted to pursue fine mapping of the qRfg1 locus. Recombinants within the qRfg1 region, screened from each backcross generation, were backcrossed to ‘Y331’ to produce the next backcross progenies. These progenies were individually genotyped and evaluated for resistance to Gibberella stalk rot. Significant (or no significant) difference in resistance reactions between homozygous and heterozygous genotypes in backcross progeny suggested presence (or absence) of qRfg1 in ‘1145’ donor fragments. The phenotypes were compared to sizes of donor fragments among recombinants to delimit the qRfg1 region. Sequential fine mapping of BC₄F₁ to BC₆F₁ generations enabled us to progressively refine the qRfg1 locus to a ~500-kb interval flanked by the markers SSR334 and SSR58. Meanwhile, resistance of qRfg1 to Gibberella stalk rot was also investigated in BC₃F₁ to BC₆F₁ generations. Once introgressed into the ‘Y331’ genome, the qRfg1 locus could steadily enhance the frequency of resistant plants by 32–43%. Hence, the qRfg1 locus was capable of improving maize resistance to Gibberella stalk rot.     

Improved tissue culture response of an elite maize inbred through backcross breeding,and identification of chromosomal regions important for regeneration by RFLP analysis

Summary The frequency of initiation of friable, embryogenic callus from immature embryos of the elite maize inbred line B73 was increased dramatically by introgression of chromosomal segments from the inbred line A188 through classical backcross breeding. Less than 0.2% of the immature B73 embryos tested (5 of 3,710) formed embryogenic callus. The breeding scheme consisted of six generations of backcrossing to B73 with selection at each generation for high frequency initiation of embryogenic cultures. BC₆ individuals were selfed for four generations to select homozygous lines. The average embryogenic culture initiation frequency increased to 46% (256/561). Nearly all (91%) of the embryos from one BC₆ S₄ plant formed embryogenic cultures. RFLP analysis was used to determine the locations and effects of the introgressed A188 chromosomal segments. Five segments were retained through at least the fifth backcross generation. The hypothesis that one or more of these five regions contains genes controlling somatic embryogenesis in maize was tested using an F₂ population of the cross A188 X Mo17. A set of five DNA markers (three of them linked) explained 82% of the observed phenotypic variance for percentage of immature embryos forming embryognic callus. Four of the five markers were located in or near introgressed A188 chromosome segments.The region marked by probe c595 on the long arm of chromosome 9 was highly associated with several measures of in vitro culture response (percent embryogenic embryos, plants per embryo, and plants per embryogenic embryo). We propose that there is a major gene (or genes) in this region in A188 that promotes embryogenic callus initiation and plant regeneration in B73, Mo17, and probably many other recalcitrant inbred lines of maize.     

Effect of the mouse scid mutation on meiotic recombination

The goal of this study was to determine the effect of the mouse severe combined immunodeficiency (scid) mutation on the rate of meiotic recombination, by standard backcross linkage analysis. For this purpose, we examined four crosses that involved F₁ hybrid animals heterozygous for the strain C57BL/6 and BALB/c genomes. In one set of reciprocal crosses, F₁ animals were homozygous scid/scid, and in a second set of reciprocal crosses, F₁ mice were homozygous wild-type (+/+) at the scid locus. Backcross progeny were typed for recombination between selected genetic markers on mouse Chromosomes (Chrs) 1, 4, 6, 7, 9, 15, and 17. Although some differences in recombination were observed over some intervals, the expression of the SCID phenotype did not appear to have a major or consistent effect on meiotic recombination. Received: 4 October 1995 / Accepted: 2 April 1996     

Immune response deficiency of BSVS mice

The genetic control of the low response of BSVS mice to streptococcal Group A carbohydrate (GAC) was studied in crosses with responder A/J mice. F₁ mice were responders. In the backcross (BSVS × A/J)F₁ × BSVS mice, there were equal numbers of anti-GAC responder and nonresponder mice, indicating genetic control by a small number of major loci. The anti-GAC responses of the backcross mice showed no obligate linkage between responder status and A/JH-2 orIgC _H alleles. However, it was observed that the average anti-GAC titers were higher in backcross mice heterozygous at these loci. The above data, a lack of low-responder F₂ animals, and the segregation of a non-H-2-, non-IgC _H -linked locus in the first and second backcross mice, indicate that the defect in the BSVS anti-GAC responsiveness involves three loci: one linked toH-2, another linked toIgC _H , and a third locus —tentatively namedIr-GAC- not linked toH-2, IgC _H , orHbb.     

Genetic regulation of alcohol dehydrogenase C2 in the mouse. Developmental consequences of the temporal locus (Adh-3t) and positioning of Adh-3 on chromosome 3

The tissue specificity of a proposed cis-acting temporal locus (Adh-3t), which regulates alcohol dehydrogenase C₂ (ADH-C₂) activity in mouse reproductive tissue extracts, has been examined in C5 7BL/6J, SM/J, F₁ (SM/J × C5 7BL/6J) mice as well as in progeny of an (F₁ [SM/J × C5 7BL/6J] × C5 7BL/6J) back-cross. Electrophoretic variants for ADH-C₂, previously used to localize the gene (Adh-3) encoding this enzyme on chromosome 3, enabled the relative parental contributions to ADH-C₂ phenotype in F¹ and backcross mouse tissues to be determined. These analyses demonstrated that (1) stomach, kidney, lung, adrenals, seminal vesicles, epididymis, uterus, and ovary ADH-C₂ is encoded by a single locus (Adh-3); Adh-3t is differentially active in various tissues, eg, lung exhibits no apparent activity whereas the temporal locus is fully active in seminal vesicles; (3) Adh-3t is probably differentically active in different cells of some tissues, eg, adrenals. Specific activity profiles of stomach and epididymal ADH-C₂ during the neonatal development of C5 7BL/6J, SM/J, and F₁ (SM/J × C5 7BL/6J) male mice supported the proposal for a cis-acting temporal locus for this enzyme. Genetic analyses examining segregation of Adh-3 and Adh-3t among backcross progeny suggested that these are distinct but closely linked loci, since one recombinant among 256 progeny was observed. Linkage data of Adh-3 with Va (varitint-waddler) and de (droopy ear) was also obtained, which suggested that Adh-3 is localized on chromosome 3 between Va and de.     

Identification and genetic mapping of 151 dispersed members of 16 ribosomal protein multigene families in the mouse

More than 150 individual members of 16 ribosomal protein multigene families were identified as DNA restriction fragments and genetically mapped. The ribosomal protein gene-related sequences are widely dispersed throughout the mouse genome. Map positions were determined by analysis of 144 progeny mice from both an interspecific (C57BL/6J × SPRET/Ei)F₁ × SPRET/Ei and an intersubspecific (C57BL/6J × CAST/Ei)F₁ × C57BL/6J backcross. In addition, 30 members of the multigene families encoding PGK1 ODC, and TPI, including five new loci for ODC and one new locus for TPI, were characterized and mapped. Interspecific backcross linkage data for 29 nonecotropic murine leukemia retroviruses endogenous to C57BL/6J mice are also reported. Transmission ratio distortions and recombination frequencies are compared between the two backcrosses.     

INDUCTION OF ASTER FORMATION AND CLEAVAGE IN EGGS OF THE SEA URCHIN HEMICENTROTUS PULCHERRIMUS BY INJECTION OF SPERM COMPONENTS*

Studies were made on which components of sperm were able to induce aster formation and cleavage of eggs of the sea urchin Hemicentrotus pulcherrimus. The sperm components were separated by homogenization and centrifugation into the following 3 fractions: the head-midpiece, midpiece and tail. The head-midpiece fraction was then divided into 2 sub-fractions, the centriole sub-fraction and the centriole-free sub-fractions. Each fraction was injected into unfertilized eggs and after 15–30 min the eggs were inseminated. The ability of a fraction or a sub-fraction to induce aster formation and cleavage was deduced from the frequency of multipolar cleavage. The head-midpiece fraction and the centriole sub-fraction were effective in inducing aster formation and cleavage, but the other fractions were not. It was concluded that isolated centrioles from sea urchin sperm act as division centers in the egg.     

Linkage of isozyme loci in the mouse: Phosphoglucomutase-2 (Pgm-2), mitochondrial NADP malate dehydrogenase (Mod-2), and dipeptidase-1 (Dip-1)

The linkages of the isozyme genes Mod-2, Pgm-2, and Dip-1 have been determined in tests with established linkage group markers among inbred strains of mice. Unique alleles for both Mod-2 and Pgm-2 have been observed in the strain of SM/J. Linkage was determined from backcross progeny of the matings C57BL/6J×(SM/J×C57BL/6J)F₁, (SM/J×SWR/J)F₁×SM/J, and (SM/J×SWR/J)F₁×SJL/J. The gene Mod-2 is on linkage group 1. In a three-point cross of the loci Gpi-1, c, and Mod-2, the c locus was determined to be the middle gene. No double crossovers were observed. Our combined data show the following linkages: Gpi-1 to c, 28.3±3.2%; Gpi-1 to Mod-2, 33.3±3.0%; and c to Mod-2, 4.1±2.8%. The proposed gene order for four markers on LG I is Gpi-1-p-c-Mod-2. The gene Pgm-2 was linked to Gpd-1 (27.0±4.2%) on LGVIII. Two backcrosses segregating for Pgm-2 and b, (SM/J×DBA/2J) F₁×DBA/2J and (SM/J×DBA/2J)F₁×C57BR/cdJ, showed 9.1±4.3% recombination. The proposed gene order on LG VIII is b-Pgm-2-Gpd-1. The genes Pgm-1 and Pgm-2 are not linked (53.4±4.4%). Linkage of the isozyme genes Dip-1 and Id-1 on LG XIII was observed in backcross progeny of the crosses (SJL/J×C57BL/6J)F₁×SJL/J and C57BL/6J×(SM/J×C57BL/6J)F₁. The combined recombination was 23.8±2.8%. Two cases are established where genes whose enzyme products share substrate affinities (Pgm-1 and Pgm-2; Mod-1 and Mod-2) are not linked. Our data generally support the conclusion that functionally or metabolically related isozyme genes are not contiguous on mouse linkage groups.This investigation was supported in part by Public Health Service General Research Support Grant GM-09966 and in part by Public Health Service Training Grant 5T01 HD-00032-07 from the National Institute of Child Health and Human Development, and by Atomic Energy Commission contract AT(30-1)-3671.     

Linkage of the Igl-1 structural and regulatory genes to Akv-2 on chromosome 16

Evidence is presented here for a close linkage between Akv-2, an ecotropic provirus found uniquely on chromosome 16 of AKR/N mice, and the immunoglobulin ₁ light chain locus, Igl-1. No recombinants between the Igl-1 locus and Akv-2 were found by Southern blot analysis of DNA obtained from progeny of the backcross of (AKR/N × SJL/J)F₁ to SJL/J, indicating that these genes map within 5.9 cM of each other. A probe specific for the flanking sequence of Akv-2 was used to detect the provirus, while one specific for the IgI-1 constant region was used to determine which allele of the structural gene was expressed in the backcross mice. The constant region of Igl-1 differs between AKR/N and SJL/J with respect to a site for the restriction endonuclease KpnI. This backcross was also used to seek recombinants between the regulatory, Igl-1r, and structural, Igl-1, loci of the immunoglobulin light chain locus, since the existence of such recombinants would prove that these loci are distinct. Since only parental types were recovered in the offspring, the structural and regulatory loci are no more than 2.3 cM apart, and the implications of this finding are discussed.Deceased.     

Sex-restricted non-Mendelian inheritance of mouse Chromosome 11 in the offspring of crosses between C57BL/6J and (C57BL/6J × DBA/2J)F1 mice

We report on the observation of sex-restricted, non-Mendelian inheritance over a region of mouse Chromosome (Chr) 11, occurring in the offspring of crosses between two commonly used Mus musculus-derived inbred strains, C57BL/6J and DBA/2J. In the surviving backcross progeny of reciprocal matings between (C57BL/6J × DBA/2J)F₁ hybrids and the C57BL/6J parental strain, we observed the preferential appearance of C57BL/6J alleles along a region of Chr 11. The deviation from Mendelian predictions was observed only in female offspring from both reciprocal backcrosses, and not in males from either cross. The sex-specificity of the observed non-Mendelian inheritance points to an explanation based on embryonic or neonatal lethality. Our data add to previously obtained evidence for a Chr 11 locus or loci with sex-specific and allele-specific effects on viability. Received: 19 December 1997 / Accepted: 10 June 1998