Interspecific comparison of ethyl methanesulfonate-induced mutation rates in relation to genome size.

A detailed presentation is made of the experimental data from the various systems used by Heddle and Athanasiou to conclude that “the relationship between mutation rate and genome size is as striking for EMS as it is for radiation, thus confirming the reality of the ABCW relation” and that “there is a relatively constant value of rec for all organisms.” It is noted that 2 of the 9 mutation rates cited came from seed treatments of higher plants and were not converted to haploid-genome mutation rates necessary for a valid comparison with other test systems. It is argued that the use of EMS-induced mutation rates from Drosophila and mouse post-meiotic male germ cells for comparisons with radiation-induced mutation rates from Drosophila and mouse spermatogonia is inappropriate. The paucity of the available data that was used is emphasized, and the dearth of all available data is recognized. The method of using the actual initially applied concentration of EMS alone as a measurement of “dose” is criticized. Nevertheless, when this procedure recommended by Heddle and Athanasiou as being necessary “to provide a consistent measure of dose” for inter-specific comparisons of EMS-induced mutation rates is applied, the papers from which the data they used were scrutinized, and other available mutation-rate data assessed, no evidence was found for a relationship between EMS-induced haploid-genome mutation rate and genome size in organisms from E. coli to H. vulgare that differ in DNA content by a factor of more than 1000. X-Ray-equivalent values differed by more than two orders of magnitude from one test system to another and by one order of magnitude for different male-germ cells of Drosophila. Our previous analysis of the available data for radiation-induced mutation rates found no relationship between mutation rate and genome size. It is considered that the failure to find a relation between EMS mutation rate and genome size from the type of analysis suggested by Heddle and Athanasiou has no bearing on the utility of the rec concept. Uncritical extrapolation from one chemical to another and to an X-ray equivalent of genetic damage has been forcefully criticized elsewhere.     

Radiation-induced forward and reverse specific locus mutations and dominant cataract mutations in treated strain BALB/c and DBA/2 male mice

Strain BALB/c and DBA/2 mice were chosen to investigate the effects of genetic background on the radiation-induced mutation rate since they exhibit differences in their radiation sensitivity. Males were exposed to 3 + 3-Gy X-irradiation and mated to untreated specific locus Test-stock females. Offspring resulting from treated spermatogonia were screened for induced specific locus forward and reverse mutations and dominant cataract mutations. Since BALB/c mice are homozygous brown and albino, specific locus forward mutations could be screened at 5 of the 7 specific loci (a, d, se, p, s), while reverse mutations could be screened at the b and c loci. Strain DBA/2 is homozygous non-agouti, brown and dilute. Therefore, specific locus forward mutations could be screened at 4 loci (c, se, p, s) and reverse mutations were screened at the a, b and d loci. Results indicate no effect of genetic background on the sensitivity to mutation induction of specific locus forward mutations, while for the dominant cataract alleles strain DBA/2 exhibited a higher mutation rate than either strain BALB/c or similarly treated (101/El X C3H/El)F1 mice. If, by confirmation, these differences should be demonstrated to be real, it is interesting that strain DBA/2 should exhibit a greater sensitivity to radiation-induced dominant mutations. First, strain DBA/2 was chosen as radiation resistant or repair competent. The observation that DBA/2 exhibited a higher sensitivity to radiation-induced mutation may indicate a role for repair, albeit misrepair, in the mutation process. Second, that the effect of genotype was only observed for the mutation rate to dominant cataract alleles may reflect a difference in the spectrum of DNA alterations which result in dominant or recessive alleles. A dominant allele is more likely misinformation, such that as heterozygote it interferes with the wild-type allele. By comparison, a recessive allele may result from any DNA alteration leading to the loss of a functional gene product. One reverse mutation at each of the a and d loci was recovered in the present experiments. The similarities of the present results for radiation-induced reverse mutations with the extensive data on the spontaneous reverse mutation rates are interesting. Reverse mutations were recovered only at the a and d loci. Further, the reverse mutations recovered at the a locus were to alternate alleles (at, Aw or Asy) while true reverse mutations were apparently recovered at the d locus.     

TolF locus in Escherichia coli: chromosomal location and relationship to loci cmlB and tolD.

The tentative map position on the Escherichia coli chromosome of the tolF locus, determining tolerance to colicins A, E2, E3, K, and L, has been confirmed by three-point transduction. It lies between the aroA and pyrD loci at about 21 min on the linkage map of Bachmann et al. (1976). The cmlB locus, determining increased resistance to the antibiotics chloramphenicol and tetracycline, also lies in this region (Reeve, 1966). Phenotypic and genetic comparison of isogenic strains that carry a mutation in either the tolF or cmlB locus makes it likely that these loci are closely related or identical. The tolD locus determining tolerance to colicins E2 and E3 as well as increased resistance to antibiotics has been reported to be located close to the aroA locus as a result of conjugation experiments (Eriksson-Grennberg et al. 1965). However, tolD did not cotransduce with any of several loci in this region, indicating that the mutation is not located within the region of the genetic map corresponding to approximately 19 to 22.5 min.     

The effect of dose fractionation on the frequency of ethylnitrosourea-induced dominant cataract and recessive specific locus mutations in germ cells of the mouse

A combined dominant cataract-recessive specific locus mutation experiment for fractionated exposure to ethylnitrosourea (2 X 80 mg/kg, 24-h fractionation interval) was designed to determine if lower doses of ethylnitrosourea are more effective in inducing dominant cataract mutations as suggested by previous results. This observation was not confirmed by the present experiment. The extensive, statistically more reliable specific locus results indicate an additive effect of fractionated ethylnitrosourea treatment. A saturable repair system for ethylnitrosourea-induced DNA damage has been previously documented (Karran et al., 1979; Sega et al., 1986; Van Zeeland et al., 1985). Two parameters inherent to a saturable system, the minimal time required for the saturated system to recover and the minimal dose to saturate the system are important, and results of experiments employing a fractionation exposure protocol must be interpreted relative to these two parameters. Longer fractionation intervals or smaller doses result in a reduced mutagenic effect. Due to the inherently lower experimental variability of the specific locus mutation assay as compared to the dominant cataract assay, the specific locus assay is the test of choice to determine factors affecting the mammalian germ cell mutation rate. The dominant cataract test requires a larger investment of experimental resources to achieve a comparable degree of accuracy. The dominant cataract mutation test is important in assessing the mutation rate to dominant alleles in germ cells of mammals. Due to the immediate expression of the mutant phenotype in newly occurring dominant mutations, a dominant mutation assay screens a genetically relevant endpoint in an assessment of the mutagenic hazard for man in mouse experiments. A multi-endpoint design screening specific locus, dominant cataract, and biochemical mutational endpoints (Ehling et al., 1985) allows a systematic comparison of mutagenic results for different classes of mutations in the same animals.     

Studies on the SAL Locus in DROSOPHILA PSEUDOOBSCURA. II. Modes of Regulation of the SAL Banding Pattern

From a consideration of genetic and chromosomal alterations which affect the banding pattern of a specific salivary chromosome region, it is concluded that (1) a regulator locus, sal, is closely linked with the region in question but separated from it spatially by a few bands; (2) either mutation of the sal locus or transfer of the region to a heterochromatic region affects the banding pattern similarly; and (3) the change probably consists of a compaction of DNA and a concomitant inactivation of genetic loci.     

Deletion mapping of kil and kor functions in the trfA and trfB regions of broad host range plasmid RK2

Figurski et al. (1982) have reported that certain loci on the broad host range plasmid RK2 (kil functions) can be cloned only in the presence of other trans-acting segments of the plasmid genome (kor functions). They have suggested that the presence of these functions may in part account for the structure of mini RK2 replicons which were constructed in order to define the regions of the plasmid which encode replication/maintenance functions (Thomas et al. 1980). We have therefore investigated the relationship between these two sets of kil and kor loci and the loci implicated in the replication/maintenance of RK2. We find that, whilst the three kil loci reported by Figurski et al. (1982) are absent from these derivatives, a fourth such locus (kilD) is closely linked to trfA, a gene essential for RK2 replication. The kilD locus was probably responsible for the inclusion in mini replicons of a segment of RK2 DNA which carries both korD and korA in addition to trfB, a gene defined by a temperature-sensitive maintenance defect, but which can be deleted leaving a functional RK2 replicon (Thomas 1981 b). The kilB locus is situated on the opposite side of kilD from trfA, all three loci lying within a 3.6 kb segment of RK2 DNA. The korA, korD and trfB functions all map within a 900 bp segment of DNA, while korB requires sequence information at least 1.5 kb from this segment.     

Heterotic trait locus (HTL) mapping identifies intra-locus interactions that underlie reproductive hybrid vigor in Sorghum bicolor

Identifying intra-locus interactions underlying heterotic variation among whole-genome hybrids is a key to understanding mechanisms of heterosis and exploiting it for crop and livestock improvement. In this study, we present the development and first use of the heterotic trait locus (HTL) mapping approach to associate specific intra-locus interactions with an overdominant heterotic mode of inheritance in a diallel population using Sorghum bicolor as the model. This method combines the advantages of ample genetic diversity and the possibility of studying non-additive inheritance. Furthermore, this design enables dissecting the latter to identify specific intra-locus interactions. We identified three HTLs (3.5% of loci tested) with synergistic intra-locus effects on overdominant grain yield heterosis in 2 years of field trials. These loci account for 19.0% of the heterotic variation, including a significant interaction found between two of them. Moreover, analysis of one of these loci (hDPW4.1) in a consecutive F2 population confirmed a significant 21% increase in grain yield of heterozygous vs. homozygous plants in this locus. Notably, two of the three HTLs for grain yield are in synteny with previously reported overdominant quantitative trait loci for grain yield in maize. A mechanism for the reproductive heterosis found in this study is suggested, in which grain yield increase is achieved by releasing the compensatory tradeoffs between biomass and reproductive output, and between seed number and weight. These results highlight the power of analyzing a diverse set of inbreds and their hybrids for unraveling hitherto unknown allelic interactions mediating heterosis.     

The Genetics of the Dras3-Roughened-Ecdysoneless Chromosomal Region (62b3-4 to 62d3-4) in Drosophila Melanogaster: Analysis of Recessive Lethal Mutations

The genetic organization of interval 62B3-4 to 62D3-4 on the Drosophila third chromosome was investigated. The region (designated DRE) includes four known loci: Roughened (R; 3-1.4), defined by a dominant mutation disrupting eye morphology; the nonvital locus Aprt, structural gene for adenine phosphoribosyltransferase; Dras3, a homolog of the vertebrate ras oncogene; and 1(3)ecdysoneless (1(3)ecd), a gene that has been implicated in the regulation of larval molting hormone (ecdysteroid) synthesis. Overlapping chromosomal deletions of the region were generated by gamma-ray-induced reversion of the R mutation. Recessive lethal mutations were isolated based upon failure to complement the recessive lethality of Df(3L)RR2, a deletion of the DRE region that removes 16-18 polytene chromosome bands. A total of 117 mutations were isolated following ethyl methanesulfonate and gamma-ray mutagenesis. These and two additional define 13 lethal complementation groups. Mutations at two loci were recovered at disproportionately high rates. One of these loci is preferentially sensitive to radiation-induced mutational alterations. Additionally, an unusually low recovery rate for cytologically detectable rearrangement breakpoints within the gamma-ray-sensitive locus suggests that an interval of the DRE region closely linked to the R locus may be dominantly sensitive to position effects. Lethal phase analysis of mutant hemizygotes indicates that a high proportion of DRE-region loci (11 of 13) are necessary for larval development. Mutations in five loci cause predominantly first-instar larval lethality, while mutations in four other loci cause predominantly second-instar lethality. Mutations in two loci cause late-larval lethality associated with abnormal imaginal disc development. A temperature-sensitive allele of one newly identified complementation group blocks ecdysteroid-induced pupariation. This developmental block is overcome by dietary 20-hydroxyecdysone, suggesting that a second locus in the region in addition to l(3)ecd may play a role in the regulation of late larval ecdysteroid levels.     

A new HaeIII polymorphism at the D21S13 locus

Summary DNA markers in the pericentromeric region of human chromosome 21 have shown linkage to a gene for Familial Alzheimer disease (FAD; St. George Hyslop et al. 1987). The limited informativeness of probes for the loci D21S13 and D21S16 have hindered precise mapping of the FAD locus and analysis of non-allelic heterogeneity in FAD (Schellenberg et al. 1988; St. George-Hyslop et al. 1987). We recently described a new EcoRII polymorphism at the D21S13 locus that was very informative in a large FAD pedigree (Pulst et al. 1990a, b). We now report another polymorphism for the D21S13 locus that further increases the informativeness of this locus.     

Deep Genome-Wide Measurement of Meiotic Gene Conversion Using Tetrad Analysis in Arabidopsis thaliana

Gene conversion, the non-reciprocal exchange of genetic information, is one of the potential products of meiotic recombination. It can shape genome structure by acting on repetitive DNA elements, influence allele frequencies at the population level, and is known to be implicated in human disease. But gene conversion is hard to detect directly except in organisms, like fungi, that group their gametes following meiosis. We have developed a novel visual assay that enables us to detect gene conversion events directly in the gametes of the flowering plant Arabidopsis thaliana. Using this assay we measured gene conversion events across the genome of more than one million meioses and determined that the genome-wide average frequency is 3.5×10⁻⁴ conversions per locus per meiosis. We also detected significant locus-to-locus variation in conversion frequency but no intra-locus variation. Significantly, we found one locus on the short arm of chromosome 4 that experienced 3-fold to 6-fold more gene conversions than the other loci tested. Finally, we demonstrated that we could modulate conversion frequency by varying experimental conditions.     

Radiation-induced untargeted germline mutations in Japanese medaka

Radiation has been shown to increase mutation frequencies at tandem repeat loci by indirect interactions of radiation with DNA. We studied germline mutations in chronically exposed Japanese medaka (Oryzias latipes) using microsatellite loci. After screening 26 randomly selected loci among unirradiated parents and their 200 offspring, we selected seven highly mutable loci (0.5-1.0 x 10(-2) mutants per locus per gamete) and two bonus loci for further study. To determine if radiation exposure increases mutation frequencies in these loci, medaka were chronically irradiated from subadults through maturation at relatively low dose rates of 68 mGy/d. Total doses for males and females were 10.4 and 3 Gy, respectively. The mean number of mutations for the offspring of exposed families (0.149+/-0.044) was significantly higher (P=0.018) than for control families (0.080+/-0.028), indicating induction of germline mutations from chronic irradiation. This increase in the microsatellite mutation rate is greater than expected from direct interaction of radiation with DNA, suggesting indirect, untargeted mechanism(s) for mutations. This study identified microsatellite loci with a high mutational background in medaka, variation among loci and families as important variables, and demonstrated the usefulness of this fish model for studying radiation-induced germline mutations.     

On the use of DNA fingerprints for linkage studies in cattle

To find a marker for the bovine "muscular hypertrophy" gene and for the "roan" locus, we have typed six cattle pedigrees totaling 540 animals for nine blood group systems, for 12 biochemical markers, for RFLPs at four loci, and with five probes revealing multilocus DNA fingerprints. Segregation analysis of the fingerprint bands showed that, in cattle, a fingerprint probe will reveal a mean of 7.6 clearly resolvable bands, behaving as simple, highly informative Mendelian entities characterized by a mean mutation rate of +/- 1/4500 gametes. For one of the bands, we observed a "mutation burst" generating germline mosaicism. Because some of the fingerprint bands were allelic or corresponded to clustered minisatellites, a mean of only 5.7 independent loci is explored per probe. Fingerprint bands revealed by different probes also show a clear propensity for close linkage, pointing toward nonrandom distribution of minisatellite sequences or the existence of minisatellite clusters. Although this reduces the power of fingerprints for linkage analysis substantially, we were able to demonstrate genetic linkage between fingerprint bands and at least three of the classical markers, to exclude the roan locus from 4.5 Morgans of the bovine genome with the DNA fingerprints and for an additional 2.5 Morgans with the classical markers, and to identify a solid candidate marker for the bovine muscular hypertrophy gene, yielding a lod score greater than or equal to 2.84 without any obliged recombinant.     

The Cross-Linking Agent Hexamethylphosphoramide Predominantly Induces Intra-Locus and Multi-Locus Deletions in Postmeiotic Germ Cells of Drosophila

The nature of DNA sequence changes induced by the cross-linking agent hexamethylphosphoramide (HMPA) within and in the vicinity of the vermilion locus of Drosophila melanogaster that produce a vermilion mutant phenotype was analyzed after exposure of postmeiotic male germ cells. Mutagenized males were mated to either females wild-type (exr(+)) for nucleotide excision repair (NER) or to females having a deficiency (exr(-)) for NER. Rearrangements, mostly deletions, represented by far the most frequent type of mutational events induced by HMPA that are detected as vermilion mutations. In the exr(+) group, all but one (a double substitution) of 21 mutants characterized were large sequence changes: we found 5 intra-locus deletions, 3 intra-locus deletions associated with insertions and 12 multi-locus deletions. When taken together, deletions and deletion/insertion mutations represent 96% of the HMPA-induced DNA modifications obtained under proficient repair conditions. Of the 10 mutants obtained from crosses with exr(-) females, 6 intra-locus and 2 multi-locus deletions were found, as opposed to just 1 point mutation and 1 double substitution. The ``hypomutability effect' observed with exr(-) genotypes in relation to the wild type seems to be caused by a decrease in the frequency of multi-locus deletions in the former group. The results suggest that the NER system is involved in the generation of multi-locus deletions, whereas intra-locus deletions appear to be formed through a postreplication slipped-misrepair pathway. It is concluded that an eukaryotic in vivo system with no limitations for the recovery of multi-locus deletions, such as vermilion, should be used for the analysis of DNA damage induced by cross-linking agents.     

Inhibition of human cytochrome P450 1B1, 1A1 and 1A2 by antigenotoxic compounds,purpurin and alizarin

Expanded simple tandem repeat (ESTR) loci include some of the most unstable DNA in the mouse genome and have been extensively used in pedigree studies of germline mutation. We now show that repeat DNA instability at the mouse ESTR locus Ms6-hm can also be monitored by single molecule PCR analysis of genomic DNA. Unlike unstable human minisatellites which mutate almost exclusively in the germline by a meiotic recombination-based process, mouse Ms6-hm shows repeat instability both in germinal (sperm) DNA and in somatic (spleen, brain) DNA. There is no significant variation in mutation frequency between mice of the same inbred strain. However, significant variation occurs between tissues, with mice showing the highest mutation frequency in sperm. The size spectra of somatic and sperm mutants are indistinguishable and heavily biased towards gains and losses of only a few repeat units, suggesting repeat turnover by a mitotic replication slippage process operating both in the soma and in the germline. Analysis of male mice following acute pre-meiotic exposure to X-rays showed a significant increase in sperm but not somatic mutation frequency, though no change in the size spectrum of mutants. The level of radiation-induced mutation at Ms6-hm was indistinguishable from that established by conventional pedigree analysis following paternal irradiation. This confirms that mouse ESTR loci are very sensitive to ionizing radiation and establishes that induced germline mutation results from radiation-induced mutant alleles being present in sperm, rather than from unrepaired sperm DNA lesions that subsequently lead to the appearance of mutants in the early embryo. This single molecule monitoring system has the potential to substantially reduce the number of mice needed for germline mutation monitoring, and can be used to study not only germline mutation but also somatic mutation in vivo and in cell culture.     

On the relationship between spontaneous mutation rates in vivo and in vitro.

Recent estimates of spontaneous mutation rates in man, in which previous sources of bias are corrected, indicate that the average is about 3 x 10(-7) per locus per generation, a much lower figure than is generally accepted. Assuming 100 to 1000 cell divisions between each gametic union, this information predicts that cellular mutation rats should be in the order of 10(-9) per locus per generation. Since none of the mutation rates measured in cultured cells are this low (average for seven characters equals 7 x 10(-7)), the size of mutation rates in cultured cells cannot be used to substantiate the claim of epigenetic inheritance. Furthermore, this information suggests that in multicellular organisms the germinal tissue is sequestered from mutagenic insult or subjected to selection against mutational damage so as to keep the genetic load of a species at a tolerable level. Alternatively, cell culture environments may present an extremely abnormal situation to somatic cells, thus elevating the mutation rate.     

Chromosomal mapping of four different integration sites of Moloney murine leukemia virus including the locus for alpha 1(I) collagen in mouse

Infection of mouse embryos with Moloney murine leukemia virus (M-MuLV) has yielded several mouse substrains with stable germ line integration of retroviral DNA at distinct chromosomal loci (Mov loci; Jaenisch et al., 1981). There is evidence that flanking DNA sequences can have an effect on virus expression and, conversely, inserted viral DNA may affect the expression of adjacent host genes. As part of our studies on the interaction of inserted M-MuLV with the mouse genome, we have chromosomally mapped four different Mov loci by hybridizing single-copy mouse sequences, flanking the proviral DNA, to interspecies somatic cell hybrids. Furthermore, these sequences were assigned regionally by in situ hybridization to mouse metaphase chromosomes. In Mov-13 mice, M-MuLV had inserted into the alpha 1(I) collagen gene leading to early embryonic death in homozygotes. We have assigned this locus to the distal region of chromosome 11. Thus, the alpha 1(I) collagen gene is part of an evolutionarily conserved linkage group with the homologous genes on human chromosome 17. Three other proviral integration sites were mapped to chromosome 1, bands BC (Mov-7), chromosome 11, bands BC (Mov-9), and chromosome 3, bands FG (Mov-10). The Mov-10-specific probe detects an EcoRI-specific restriction fragment length polymorphism, which can make this probe a useful genetic marker.     

Likelihood analysis of disequilibrium mapping, and related problems.

In this paper a theory is developed that provides the sampling distribution of alleles at a diallelic marker locus closely linked to a low-frequency allele that arose as a single mutant. The sampling distribution provides a basis for maximum-likelihood estimation of either the recombination rate, the mutation rate, or the age of the allele, provided that the two other parameters are known. This theory is applied to (1) the data of Hästbacka et al., to estimate the recombination rate between a locus associated with diastrophic dysplasia and a linked RFLP marker; (2) the data of Risch et al., to estimate the age of a presumptive allele causing idiopathic distortion dystonia in Ashkenazi jews; and (3) the data of Tishkoff et al., to estimate the date at which, at the CD4 locus, non-African lineages diverged from African lineages. We conclude that the extent of linkage disequilibrium can lead to relatively accurate estimates of recombination and mutation rates and that those estimates are not very sensitive to parameters, such as the population age, whose values are not known with certainty. In contrast, we also conclude that, in many cases, linkage disequilibrium may not lead to useful estimates of allele age, because of the relatively large degree of uncertainly in those estimates.     

Evolutionary transience of hypervariable minisatellites in man and the primates.

Using PCR, two minisatellite loci showing extreme repeat-unit copy-number variation in humans have been characterized in great apes and monkeys. In contrast to humans, minisatellite locus MS32 is monomorphic with only 3-4 diverged repeat units in great apes, Old World and New World monkeys, this organization presumably representing the relatively stable ancestral precursor state of the human hypervariable locus. Similarly, minisatellite MS1 shows extreme repeat-copy-number variability in man compared with low copy number and minimal variability in great apes. Analysis of variant repeat units shows that the 5' and 3' regions of MS1 are relatively stable in great apes and man, and that variability in man is confined to the central region of the minisatellite. In contrast to the great apes, MS1 is highly variable in Old World monkeys. These results, as well as computer simulations of minisatellite evolution based on known mutation rates, show that short minisatellites are stable within the genome, and that the degree of polymorphism at a given locus can change dramatically over a short period of evolutionary time. The ability of hypervariable minisatellites to detect highly informative loci by cross-species hybridization is therefore largely unpredictable.     

Linkage relationships among 20 genetic markers in cattle. Evidence for linkage between two pairs of blood group systems: B-Z and S-F/V respectively

Five bovine paternal half-sib pedigrees for a total of 527 individuals were typed for six blood group systems: A, B, F/V, L, S, Z; for nine biochemical polymorphisms: ADA, MPI, PGM-3(slow), NP, Gc, Pi2, Tf, Ptf1 and Ptf2; and for restriction fragment length polymorphisms at five autosomal loci: Tg, GH, LDLr, BoLA-DQ and BoLA-DY. Two of the pedigrees were informative for segregation at the 'muscular hypertrophy' locus, and one was informative at the coat colour determining 'roan' locus. Linkage analysis was performed between all markers. Linkage was demonstrated between the S and F/V blood group systems (z = 3.11), adding one locus to the previously identified linkage group VII (LGVII) [Pi-2 and S], the most likely order being Pi2-S-F/V with maximum likelihood recombination rates of 0.208 and 0.211. Also shown to be linked were the blood group systems B and Z (z = 5.7, theta = 0.245). We confirmed the observation previously made by Andersson et al. (1988) of a high recombination rate between class II genes DQ and DY, suggesting either a larger physical distance between those genes than expected from comparative data, or the presence of a 'recombinational hotspot' in the bovine major histocompatibility complex. No linkage was found either with the 'muscular hypertrophy' locus, or with the 'roan' locus. However, these two loci could be excluded from respectively 1.7 and 2.5 Morgans of the bovine genome.     

A linkage study of Emery-Dreifuss muscular dystrophy

Summary We have searched for linkage between polymorphic loci defined by DNA markers on the X chromosome and X-linked Emery-Dreifuss muscular dystrophy (EDMD). There are high recombination rates between EDMD and the Xp loci known to be linked to Becker and Duchenne muscular dystrophy. There is a suggestion of linkage between EDMD and the loci DXS52 and DXS15, defined by probes St 14 and DX13 respectively, located at Xq28. for DXS15=1.14 at =0.15. This is in agreement with the previously reported linkage between a disorder strongly resembling EDMD and colour-blindness (Thomas et al. 1972), suggesting that there is a second locus on the X chromosome concerned with muscle integrity.