Genetic Linkage between the AH Locus and a Major Gene That Inhibits Susceptibility to Audiogenic Seizures in Mice

Mice of the DBA/2 (D2) strain are highly susceptible to sound-induced seizures at 21 days of age; whereas, mice of the C57BL/6 (B6) strain are resistant to these seizures. Although the difference in susceptibility to audiogenic seizures (ASs) between these two strains is inherited as a multiple-factor trait, an association was observed between susceptibility to ASs and the Ah locus. The Ah locus controls the inducibility of aryl hydrocarbon hydroxylase (AHH) activity by a number of aromatic hydrocarbons. B6 mice carry the Ah^b allele and have inducible AHH activity; whereas, D2 mice carry the Ah^d allele and have noninducible activity. Inducibility is inherited as a Mendelian dominant trait in crosses between these strains. Mice carrying the Ah^b allele are generally less susceptible to ASs at 21 days of age than are mice carrying the Ah^d allele. The combined results from B6 x D2 recombinant inbred strains, congenic strains (where the Ah^b allele was placed into the D2 genome and the Ah^d allele placed into the B6 genome), the B6D2F₁ x D2 backcross generation, and a random survey of various inbred strains, suggest that the association between these two traits is due to genetic linkage, rather than to pleiotrophy or to chance. A major gene that inhibits susceptibility to ASs appears to be closely linked to the Ah locus. This gene has been designated Ias, for inhibition of ASs. A large portion of the genetic variability of AS susceptibility may be due to the segregation of Ias.     

Genetic Analysis of Nucleotide Triphosphatase Activity in the Mouse Brain

A Ca(2+)- or Mg(2+)-stimulated ecto-ATPase is thought to regulate the hydrolysis of extracellular ATP in nervous tissues. The hydrolysis of nucleotide triphosphates (NTPs) was analyzed in brain microsomal fractions from crosses of DBA/2J (D2) and C57BL/6J (B6) mice. The nucleotide triphosphatase (NTPase) activity was significantly reduced in D2 mice as compared to B6 mice, and B6D2F(1) hybrids had activities intermediate to the parentals. A significant positive correlation was found between the hydrolysis of four NTPs (ATP, CTP, GTP and UTP) in 24 B6 X D2 (BXD) recombinant inbred (RI) strains of mice and in 80 B6D2F(1) X D2 backcross mice. The RI strains and backcross mice fell into two distinct groups with respect to the NTPase activity. Linkage of NTPase activity was suggested with the chromosome 2 markers, D2Mit6 and Ass-1, in the RI strains, and was confirmed by analysis of other markers in the backcross population. These data suggest that the Ca(2+)- or Mg(2+)-stimulated hydrolysis of NTPs, designated Ntp, is regulated by a single gene located on proximal chromosome 2. Although an association was observed previously between Ca(2+)-ATPase activity and susceptibility to audiogenic seizures (AGS), no significant association was observed for the expression of Ntp and AGS susceptibility.     

Genetic Variation at a Locus (TAM-1) for Submaxillary Gland Protease in the Mouse and Its Location on Chromosome 7

Electrophoretic and activity variants for a testosterone-induced esteroprotease have been discovered in submaxillary glands from inbred strains of mice. The enzyme is tentatively designated tamase (TAM-1) and the variant genetic locus is Tam-1. The alleles Tam-1^a and Tam-1^b determine electrophoretically distinct zones of tamase activity, while Tam-1^c produces no detectable enzyme activity. Data from recombinant inbred strains and B6AF₁ x B6 and B6D2F₁ x B6 backcrosses established linkage of Tam-1 to glucose phosphate isomerase (Gpi-1), pink-eyed dilution (p) and β-hemoglobin (Hbb) on chromosome 7. The gene order is Gpi-1—Tam-1—p—Hbb. Analysis of congenic resistant strains indicates that Tam-1 is closely linked to the minor histocompatibility locus, H-4. TAM-1 was not cross-reactive with antisera to mouse nerve growth factor, submaxillary renin, or tamases A and D.     

Genetic Study of Cationic ATPase Activities and Audiogenic Seizure Susceptibility in Recombinant Inbred and Congenic Strains of Mice

Total, Mg2+, and Na+, K+ ATPase activities were studied in fresh brain homogenates of the audiogenic seizure (AGS)-resistant C57BL/6J (B6) and AGS-susceptible DBA/2J (D2) inbred strains and in 13 B6 X D2 (BXD) recombinant inbred (RI) strains. These activities were also studied in the D2.B6-Iasb congenic mice, that are similar genetically to D2 mice, except for the Iasb gene which inhibits the spread of AGS activity. The total and Mg2+ ATPase activities of the brainstem were significantly lower in the D2 than in the B6 mice at 21 days of age. No differences were found between these strains for Na+,K+ ATPase activity. The total, Mg2+, and Na+,K+ ATPase activities in the B6 brainstem did not change noticeably from 21 to 80 days of age. In the D2 brainstem, however, the Mg2+ activity increased with age, and the Na+,K+ ATPase activity decreased from 30 to 80 days of age. No genetic associations could be found between AGS susceptibility and total or Mg2+ ATPase activities in the D2.B6-Iasb mice or among the 13 BXD RI strains. Hence, differences in genetic background, rather than differences in AGS susceptibility, can account for the lower ATPase activities in 21-day-old D2 mice. Further, the Mg2+ and Na+,K+ ATPase activities appear to be regulated by more than one gene. This study emphasizes the utility of RI and congenic strains for testing the biochemical basis of AGS susceptibility in mice.     

Genes for Dwarfness in Wheat, TRITICUM AESTIVUM L

The genetic control of plant height was studied in crosses of four spring wheats involving the standard height variety Ramona 50 and short-statured selections Olesen, D6301, and D6899. Data from parent, F₁, F₂, and F₃ populations indicated that four independently segregating loci account for most of the differences among the four varieties. Two major genes of a highly recessive nature condition reduced height in Olesen and the Norin 10 derivative D6301. Olesen also carries a third dwarfing gene which is partially dominant in its effects over genes for tallness. This gene, or a gene that acts in a similar manner, is also present in the standard height variety Ramona 50. Dwarfing in D6899, a derivative of Tom Thumb, is controlled primarily by a single gene with mainly additive effects which is not present in any of the other three varieties.

Genetic components estimated from generation means (parental, F₁, F₂, F₃, and backcross) indicated that additive gene effects were the major component of variation in four of the six crosses, and of similar magnitude to dominance effects in another cross. The primary source of genetic variation in the cross Olesen x D6899 was due to epistasis with both additive x additive and dominance x dominance effects of major importance. The results of the generation mean analyses were consistent with the models for major-gene control of plant height based on segregation patterns.

     

Cytogenetic analysis of pseudolinkage of ldh Loci in the teleost genus salvelinus

Cytological and genetic analyses provide evidence that spontaneous centric fusion and fission can account for curious patterns of pseudolinkage of two LDH loci in males of brook trout (Salvelinus fontinalis) and in the F₁, F₂ and backcross generations of lake trout (S. namaycush) x brook trout hybrids. Intraindividual polymorphisms for acrocentric and metacentric chromosomes in somatic and gonadal tissue of these fish have been related to the proposed polyploid evolution in Salmonidae.     

Localization to chromosome 10 of a locus influencing morphine analgesia in crosses derived from C57BL/ and DBA/2 strains

A quantitative trait locus (QTL) was detected and mapped to proximal chromosome 10 near the markers Mpmv5 and D10Mit51 with a strong influence on morphine-induced analgesia in the BXD recombinant inbred (Rl) strains and in an F₂ cross (B6D2F2) between the BXD progenitor strains, C57BL/6 and DBA/2. A LOD score of 3.9 (p <. 00002) was seen for analgesia using the hot plate assay. Naloxone Bmax was also associated with this chromosome region in BXD RI mice. The mu opioid receptor gene (Oprm) has recently been mapped to this same chromosome region. The observation that several morphine-related traits and naloxone Bmax appear to be partly determined by this presumed single locus is consistent with the hypothesis that the mu opioid receptor gene, or one of its modulators, is the basis for the QTL.     

High genetic susceptibility to ethanol withdrawal predicts low ethanol consumption

C57BL/6J (B6) inbred mice are well known to drink large amounts of alcohol (ethanol) voluntarily and to have only modest ethanol-induced withdrawal under fixed dose conditions. In contrast, DBA/2J (D2) mice are ``teetotallers' and exhibit severe ethanol withdrawal. Speculation that an inverse genetic relationship existed between these two traits was substantiated by meta-analysis of existing data collected in multiple genetic models, including large panels of standard and recombinant inbred strains, their crosses, and selectively bred mouse lines. Despite methodological differences among laboratories in measurement of both preference drinking and withdrawal, a nearly universal finding was that genotypes consuming large amounts of 10% ethanol (calculated as g/kg/day) during two-bottle choice preference drinking were genetically predisposed to low withdrawal scores in independent studies after either acute or chronic ethanol treatment. Conversely, low-drinking genotypes had higher withdrawal severity scores. The genetic relationship appears to be strongest in populations derived from B6 and D2, where data from more genotypes (BXD RIs, B6D2F₂s, BXD RI F₁s, and B6D2F₂-derived selectively bred lines) were available for analysis. Gene mapping studies in these populations identified four chromosome regions [on Chromosomes (Chrs) 1, 2, 4, and 15] where genes might potentially influence both traits. Among genotypes with greater genetic diversity (for example, a panel of standard inbred strains or selectively bred lines), the relationship was less pronounced. Thus, reduced susceptibility to the development of high alcohol use may be supported by increased genetic susceptibility to ethanol withdrawal symptoms. Received: 15 September 1998 / Accepted: 8 October 1998     

Intersubspecific subcongenic mouse strain analysis reveals closely linked QTLs with opposite effects on body weight

A previous genome-wide QTL study revealed many QTLs affecting postnatal body weight and growth in an intersubspecific backcross mouse population between the C57BL/6J (B6) strain and wild Mus musculus castaneus mice captured in the Philippines. Subsequently, several closely linked QTLs for body composition traits were revealed in an F₂ intercross population between B6 and B6.Cg-Pbwg1, a congenic strain on the B6 genetic background carrying the growth QTL Pbwg1 on proximal chromosome 2. However, no QTL affecting body weight has been duplicated in the F₂ population, except for mapping an overdominant QTL that causes heterosis of body weight. In this study, we developed 17 intersubspecific subcongenic strains with overlapping and nonoverlapping castaneus regions from the B6.Cg-Pbwg1 congenic strain in order to search for and genetically dissect QTLs affecting body weight into distinct closely linked loci. Phenotypic comparisons of several developed subcongenic strains with the B6 strain revealed that two closely linked but distinct QTLs that regulate body weight, named Pbwg1.11 and Pbwg1.12, are located on an 8.9-Mb region between D2Mit270 and D2Mit472 and on the next 3.6-Mb region between D2Mit205 and D2Mit182, respectively. Further analyses using F₂ segregating populations obtained from intercrosses between B6 and each of the two selected subcongenic strains confirmed the presence of these two body weight QTLs. Pbwg1.11 had an additive effect on body weight at 6, 10, and 13?weeks of age, and its castaneus allele decreased it. In contrast, the castaneus allele at Pbwg1.12 acted in a dominant fashion and surprisingly increased body weight at 6, 10, and 13?weeks of age despite the body weight of wild castaneus mice being 60% of that of B6 mice. These findings illustrate the complex genetic nature of body weight regulation and support the importance of subcongenic mouse analysis to dissect closely linked loci.     

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     

Control of the antibody response of C57BL/6 Lyt-congenic strains to the Lyt-3.1 alloantigen by a gene linked to theLyt-2 locus

Congenic anti-Lyt-3.1 sera have recently been produced by immunizing B6-Lyt-2^a mice with thymocytes from either B6-Lyt-2^a, Lyt-3^a or B6-Lyt-2^a, Lyt-3^a, H-2^k mice (Boos et al. 1978). Surprisingly, mice of the congenic strain B6 failed to produce either anti-Lyt-2.1 or anti-Lyt-3.1 cytotoxic antibodies after identical immunizations. To determine the genetic basis for the difference in response to Lyt-3.1, (B6 × B6-Lyt-2^a)F_a mice and progeny of the backcross, (B6 × B6-Lyt-2^a)F₁ × B6-Lyt-2^a, were immunized with B6-Lyt-2^a, Lyt-3^a, H-2^k thymocytes. In addition, thymic biopsies of backcross progeny were performed and thymocytes tested for the Lyt-2.2 antigenic specificity. Results indicate that gene(s) governing the immune response to Lyt-3.1 is (are) linked to theLyt-2 locus, and that the responder allele (linked toLyt-2 ^a ) shows very poor penetrance in Lyt-2^a/Lyt-2^b mice.     

Control of UVB immunosuppression in the mouse by autosomal and sex-linked genes

Irradiation with UVB (290–320 nm) initiates a systemic immunosuppression detectable as suppression of contact hypersensitivity (CHS). We investigated susceptibility to UV suppression in reciprocal F₁-hybrid and backcross mice derived from BALB/c (low susceptibility) and C57BL/6 (high susceptibility) inbred strains. CB6F₁ male mice exhibited high susceptibility and B6CF₁ male mice exhibited low susceptibility, indicating a major X-linked effect in the genetic control of UV immune suppression. Females of either F₁ hybrid showed intermediate suppression, consistent with random X-inactivation. A model of monogenic X-linked control was not sufficient, and evidence for the action of two genetically unlinked autosomal genes was found in parental backcross animals. Both sexes of (BALB/c × CB6F₁) mice showed a 1 high: 1 low ratio of phenotypes, indicating control by a major autosomal locus, Uvs1, confirmed by propagation of the high phenotype through selective backcrossing for nine generations to BALB/c. Uvs1 was not genetically linked to 12 chromosomal markers including the pigment genes b (brown) and c (albino). Backcross animals (C57BL/6 × CB6F₁) showed a significant sex difference, male mice giving a 3 high: 1 low ratio of phenotypes, compatible with the action of a second autosomal locus, Uvs2, in this hybrid. The findings are compatible with a model in which high phenotype (Uvs1 ^b/Uvs1 ^b) is dominant when subjected to recessive epistatis by the X-chromosome locus Uvs3, or by the autosomal locus Uvs2. The finding of genetic control by interacting autosomal and X-linked genes is unique. Genetically determined high susceptibility to UV immunosuppression may be an important risk factor for UV-related human diseases.     

Mapping of theLyb-4 gene to different chromosomes in DBA/2J and C3H/HeJ mice

Linkage has been established between the Lyb-4 alloantigen locus and the chromosome 4 markersLyb- 2 andMup- 1 using recombinant inbred (RI) strains. Only 2 of 24 BXD RI strains possess recombinant genotypes with respect to the B cell alloantigen lociLyb- 4 andLyb- 2, for an estimated recombination frequency of 0.024 ±0.019. One additional BXD RI strain was a recombinant with respect toLyb- 4 andMup- 1 (major urinary protein locus) for an estimated recombination frequency of 0.039 ± 0.026. These linkages were confirmed and further quantitated in a (C57BL/6J × DBA/2J)F₁ × C57BL/6J backcross population, in which the recombination frequency betweenLyb- 4 andMup- 1 was 0.049 ± 0.019. No recombination between the expression of Lyb-4.1 antigen and the ability of anti-Lyb-4.1 serum to suppress MLC reactivity was found, indicating that the genes controlling the antigenic determinant which is recognized with cytotoxic antibodies in anti-Lyb-4.1 serum is the same as, or is very closely linked to, the gene which is responsible for augmentation of the MLC response. In contrast, no linkage was observed between the gene controlling the Lyb-4.1 determinant andMup- 1 in RI strain and backcross mice derived from the cross of C3H/HeJ and C57BL/6J. Again, there was complete concordance between the serologically recognized determinant and the ability of anti-Lyb-4.1 serum to suppress the MLC response. Absorption of anti-Lyb-4.1 serum with C3H/HeJ, DBA/2J, and C57BL/6J lymphocytes, followed by the cytotoxic assay of the absorbed sera on lymphocytes of each of these three strains showed that serologically the Lyb-4.1 antigenic determinant on DBA/2 mice was indistinguishable from that on C3H/HeJ mice. Thus, both traits appear to be under the control of single genes in both DBA/2J and C3H/HeJ, but the C3H/HeJ gene appears to be nonallelic and unlinked to the DBA/2J gene.Abbreviations used in this paper LAD lymphocyte activating determinants - LPS lipopolysaccharide - MLC mixed lymphocyte culture - RI recombinant inbred     

Murine responses to (Tyr-Glu-Ala-Gly)n: II. H-2 and non-H-2 gene effects

Mice of the H-2^b haplotype responded to the sequential polymer poly(Tyr-Glu-Ala-Gly) in the in vitro T-cell proliferative assay, irrespective of whether they were homozygous or heterozygous at the H-2^b locus. The antibody responses of the H-2^b congenic mice to this polymer were variable, with A.BY and BALB.B showing responses better than those of C57BL/6 and C57BL/10 strains. The antibody responses of the F₁ progeny of (responder × nonresponder) strains of mice to this polymer are generally lower than the responder parents. F₁ mice with C57BL/10 background were the poorest responders. Studies with F₂ mice and backcross progenies of selective breeding of high and low antibody responder (C57BL/6 × BALB/c) F₁ to high responder C57BL/6 mice indicated that both non-H-2 genes and H-2 gene dosage effects influenced the magnitude of the humoral antibody responses. Animals having low responder non-H-2 background and only half the dosage of the responder immune response genes has greatly diminished antibody responses.     

Traits That Influence Longevity in Mice

Analysis of genetic interactions in the segregating backcross [(C57BL/6 x DBA/2)F₁ x DBA/2] mice revealed influences of genetic and environmental factors on life span. Using determinants of coat color (brown locus of chromosome 4 and dilute locus of chromosome 9), serologically determined H-2 antigens (chromosome 17 ) and sex as genetic markers, we studied the effects of these genes on longevity. The results suggested that genes in the brown locus (b) segment of chromosome 4, genes in a segment of the sex chromosomes and, to a more limited extent, genes in the segment of chromosome 17 which contains the H-2 haplotype all influenced longevity. The coat color (b locus) segment of chromosome 4 was associated with life span predominantly in females, whereas the chromosome 17 (H-2 haplotype) segment was associated with longer life primarily in males. The dilute locus d segment on chromosome 9 did not affect life span. Longevity appears to be influenced by interactions between genes in the chromosomal segment carrying H-2, those in the b segment, gender and the month of birth. Greater heterozygosity at the loci studied was associated with longer life span. Histopathological findings on mice that died at or after 28 months of age were comparable for all genetic combinations except that there was an increased frequency of lymphoma in females and an increased frequency of amyloidosis in males. Our analysis emphasizes the need for comprehensive studies of aging and longevity that would simultaneously determine the effects of several genetic regions and their interactions with the environment with respect to possible causes of death.     

Odorant-binding proteins OBP57d and OBP57e affect taste perception and host-plant preference in Drosophila sechellia

Despite its morphological similarity to the other species in the Drosophila melanogaster species complex, D. sechellia has evolved distinct physiological and behavioral adaptations to its host plant Morinda citrifolia, commonly known as Tahitian Noni. The odor of the ripe fruit of M. citrifolia originates from hexanoic and octanoic acid. D. sechellia is attracted to these two fatty acids, whereas the other species in the complex are repelled. Here, using interspecies hybrids between D. melanogaster deficiency mutants and D. sechellia, we showed that the Odorant-binding protein 57e (Obp57e) gene is involved in the behavioral difference between the species. D. melanogaster knock-out flies for Obp57e and Obp57d showed altered behavioral responses to hexanoic acid and octanoic acid. Furthermore, the introduction of Obp57d and Obp57e from D. simulans and D. sechellia shifted the oviposition site preference of D. melanogaster Obp57d/e^KO flies to that of the original species, confirming the contribution of these genes to D. sechellia's specialization to M. citrifolia. Our finding of the genes involved in host-plant determination may lead to further understanding of mechanisms underlying taste perception, evolution of plant–herbivore interactions, and speciation.     

Asymmetrical reinforcement and Wolbachia infection in Drosophila

Reinforcement refers to the evolution of increased mating discrimination against heterospecific individuals in zones of geographic overlap and can be considered a final stage in the speciation process. One the factors that may affect reinforcement is the degree to which hybrid matings result in the permanent loss of genes from a species' gene pool. Matings between females of Drosophila subquinaria and males of D. recens result in high levels of offspring mortality, due to interspecific cytoplasmic incompatibility caused by Wolbachia infection of D. recens. Such hybrid inviability is not manifested in matings between D. recens females and D. subquinaria males. Here we ask whether the asymmetrical hybrid inviability is associated with a corresponding asymmetry in the level of reinforcement. The geographic ranges of D. recens and D. subquinaria were found to overlap across a broad belt of boreal forest in central Canada. Females of D. subquinaria from the zone of sympatry exhibit much stronger levels of discrimination against males of D. recens than do females from allopatric populations. In contrast, such reproductive character displacement is not evident in D. recens, consistent with the expected effects of unidirectional cytoplasmic incompatibility. Furthermore, there is substantial behavioral isolation within D. subquinaria, because females from populations sympatric with D. recens discriminate against allopatric conspecific males, whereas females from populations allopatric with D. recens show no discrimination against any conspecific males. Patterns of general genetic differentiation among populations are not consistent with patterns of behavioral discrimination, which suggests that the behavioral isolation within D. subquinaria results from selection against mating with Wolbachia-infected D. recens. Interspecific cytoplasmic incompatibility may contribute not only to post-mating isolation, an effect already widely recognized, but also to reinforcement, particularly in the uninfected species. The resulting reproductive character displacement not only increases behavioral isolation from the Wolbachia-infected species, but may also lead to behavioral isolation between populations of the uninfected species. Given the widespread occurrence of Wolbachia among insects, it thus appears that there are multiple ways by which these endosymbionts may directly and indirectly contribute to reproductive isolation and speciation.     

Strain distribution pattern in AXB and BXA recombinant inbred strains for loci on murine Chromosomes 10, 13, 17, and 18

Strain distribution patterns (SDPs) of selected loci previously mapped to murine Chromosomes (Chrs) 10, 13, 17, and 18 are reported for the AXB, BXA recombinant inbred (RI) strain set derived from the progenitor strains A/J (A) and C57BL/6J (B). The loci included the simple sequence length polymorphisms (D10Nds1, D10Mit2, D10Mit10, D10Mit14, D13Mit3, D13Nds1, D13Mit10, D13Mit13, D13Mit7, D13Mit11, D17Mit18, D17Mit10, D17Mit20, D17Mit3, D17Mit2, D18Mit17, D18Mit9, and D18Mit4), the restriction fragment length polymorphisms Pdea and Csfmr, and the biochemical marker AS-1. These loci were chosen because they map to genomic regions that had few or no genetic markers in the AXB, BXA RI set. Several of these loci also were typed in backcross progeny of matings of the (AXB)F₁ to strain A or B. The strain distribution patterns for chromosomes 10, 13, 17, and 18 are reported, and the gene order and map distances determined from the backcross data. The addition of these markers to the AXB, BXA RI strain set increases the genomic region over which linkage for new markers can be detected.     

Genetics of Heading Time in Wheat (TRITICUM AESTIVUM L.). II. the Inheritance of Vernalization Response

The inheritance of vernalization response was studied in crosses involving four spring wheats (Sonora 64 (S), Pitic 62 (P), Justin (J) and Thatcher (T)) and three winter wheats (Blackhull (B), Early Blackhull (E) and Extra Early Blackhull (EE)).—All winter cultivars were highly responsive to vernalization, and Pitic 62 was the only spring cultivar whose time to heading was significantly accelerated following cold treatments. When vernalized and grown under long days, spring and winter cultivars became comparable in their heading response, indicating that cold requirement is the major attribute differentiating the heading behavior of true spring and true winter wheats.—Inheritance of growth habit in the F₁ generation of a five-parent diallel cross showed dominance of the spring character in all spring x winter crosses. Depending on the cross, one or two duplicate major genes governing growth habit were detected in F₂, F₃ and backcross generations grown in the field under long days in the absence of vernalizing temperatures. In some spring x winter crosses most of the variation in heading time among spring segregates could be attributed to the effects of major genes conditioning growth habit. In other crosses the heading patterns appeared more complex, indicating that genes with smaller effects are also involved in the control of heading response under spring or summer environments.—Evidence was presented supporting the hypothesis that the cultivar Pitic 62 carries a different allele at one of the two major loci governing its spring habit. This allele was associated with some response to vernalization and acted as a dominant gene determining earliness under low temperature vernalization, but as a partially recessive gene determining lateness in the absence of vernalizing temperatures. Genotypes were assigned to five cultivars as follows: S, CC DD; P, CC D'D'; J, cc DD; B and EE, cc dd.—The presence of major and minor genes and of multiple alleles governing response to photoperiod and vernalization was discussed in relation to the genetic manipulation of the heading response and to breeding wheat cultivars with specific or broad adaptation.     

Identification of Hepatocarcinogen-Resistance Genes in Dba/2 Mice

Male DBA/2J mice are ~20-fold more susceptible than male C57BL/6J mice to hepatocarcinogenesis induced by perinatal treatment with N,N-diethylnitrosamine (DEN). In order to elucidate the genetic control of hepatocarcinogenesis in DBA/2J mice, male BXD recombinant inbred, D2B6F(1) X B6 backcross, and D2B6F(2) intercross mice were treated at 12 days of age with DEN and liver tumors were enumerated at 32 weeks. Interestingly, the distribution of mean tumor multiplicities among BXD recombinant inbred strains indicated that hepatocarcinogen-sensitive DBA/2 mice carry multiple genes with opposing effects on the susceptibility to liver tumor induction. By analyzing D2B6F(1) X B6 backcross and D2B6F(2) intercross mice for their liver tumor multiplicity phenotypes and for their genotypes at simple sequence repeat marker loci, we mapped two resistance genes carried by DBA/2J mice, designated Hcr1 and -2, to chromosomes 4 and 10, respectively. Hcr1 and Hcr2 resolved the genetic variance in the backcross population well, indicating that these resistance loci are the major determinants of the variance in the backcross population. Although our collection of 100 simple sequence repeat markers allowed linkage analysis for ~95% of the genome, we failed to map any sensitivity alleles for DBA/2J mice. Thus, it is likely that the susceptibility of DBA/2J mice is the consequence of the combined effects of multiple sensitivity loci.