The locus for apolipoprotein E (apoE) is close to the Lutheran (Lu) blood group locus on chromosome 19

Summary Linkage has been described between the loci for apolipoprotein E (apoE) and the complement C3 (C3) on chromosome 19. C3 is known to belong to a linkage group with gene order C3-Se-Lu. The present study revealed linkage between Se and apoE with peak lod score +3.3 at recombination fraction 0.08 in males and +1.36 at 0.22 in females, and linkage between apoE and Lu with lod score +4.52 at zero recombination in sexes combined. The C3-apoE linkage gives lod score +4.00 at = 0.18 in males, but +0.04 at =0.45 in females. Triple heterozygote families confirm that apoE is on the Se side and on the Lu side of C3. Allelic association between apoE and Lu has not been ruled out. Combining our data with published data on C3-Se and Se-Lu, this segment of chromosome 19 has an average sex ratio of female/male recombination of 2.3.     

The locus for apolipoprotein CII is closely linked to the apolipoprotein E locus on chromosome 19 in man

Summary We have demonstrated close linkage between the genes for apolipoprotein E (apoE) and apolipoprotein CII (apoCII). Families segregating for apoE protein variants were screened for a DNA restriction fragment length polymorphism close to the apoCII gene by using an apoCII cDNA clone. The maximum lod score is 4.52 (sexes combined) at a recombination frequency of zero. Given linkage, it may be assumed that no recombinations have happened in altogether 33 observed meioses. It is therefore evident that the apoCII gene is situated on chromosome 19, close to the apoE gene.     

Recombination between rhodopsin and locus D3S47 (C17) in rhodopsin retinitis pigmentosa families

Autosomal dominant retinitis pigmentosa (adRP) has shown linkage to the chromosome 3q marker C17 (D3S47) in two large adRP pedigrees known as TCDM1 and adRP3. On the basis of this evidence the rhodopsin gene, which also maps to 3q, was screened for mutations which segregated with the disease in adRP patients, and several have now been identified. However, we report that, as yet, no rhodopsin mutation has been found in the families first linked to C17. Since no highly informative marker system is available in the rhodopsin gene, it has not been possible to measure the genetic distance between rhodopsin and D3S47 accurately. We now present a linkage analysis between D3S47 and the rhodopsin locus (RHO) in five proven rhodopsin-retinitis pigmentosa (rhodopsin-RP) families, using the causative mutations as highly informative polymorphic markers. The distance, between RHO and D3S47, obtained by this analysis is theta = .12, with a lod score of 4.5. This contrast with peak lod scores between D3S47 and adRP of 6.1 at theta = .05 and 16.5 at theta = 0 in families adRP3 and TCDM1, respectively. These data would be consistent with the hypothesis that TCDM1 and ADRP3 represent a second adRP locus on chromosome 3q, closer to D3S47 than is the rhodopsin locus. This result shows that care must be taken when interpreting adRP exclusion data generated with probe C17 and that it is probably not a suitable marker for predictive genetic testing in all chromosome 3q-linked adRP families.     

The gene for trypsin inhibitor CMe is regulated in trans by the lys 3a locus in the endosperm of barley (Hordeum vulgare L.)

Summary A cDNA encoding trypsin inhibitor CMe from barley endosperm has been cloned and characterized. The longest open reading frame of the cloned cDNA codes for a typical signal peptide of 24 residues followed by a sequence which is identical to the known amino acid sequence of the inhibitor, except for an Ile/Leu substitution at position 59. Southern blot analysis of wheat-barley addition lines has shown that chromosome 3H of barley carries the gene for CMe. This protein is present at less than 2%–3% of the wild-type amount in the mature endosperm of the mutant Risø 1508 with respect to Bomi barley, from which it has been derived, and the corresponding steady state levels of the CMe mRNA are about I%. One or two copies of the CMe gene (synonym Itc1) per haploid genome have been estimated both in the wild type and in the mutant, and DNA restriction patterns are identical in both stocks, so neither a change in copy number nor a major rearrangement of the structural gene account for the markedly decreased expression. The mutation at the lys 3a locus in Risø 1508 has been previously mapped in chromosome 7 (synonym 5H). A single dose of the wild-type allele at this locus (Lys 3a) restores the expression of gene CMe (allele CMe-1) in chromosome 3H to normal levels.     

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.     

Cold-sensitive chromosome regions and heterochromatin inCestrum (Solanaceae):C. strigillatum,C. fasciculatum,andC. elegans

Cold-induced mitotic under-condensation of certain chromosome segments is a rare phenomenon in plants. There are about 11 genera of monocotyledons and only 3 of dicotyledons, where species are known to have such cold-sensitive regions (CSRs). The molecular causes of cold-induced undercondensation are not clear, and no consistent cytochemical characteristics of CSRs are known. Recently we have presented a chromosome banding analysis on CSRs and their relation to constitutive heterochromatin inCestrum parqui (Solanaceae), a species of sect.Cestrum. The present study is concerned with a similar analysis inC. strigillatum of sect.Cestrum, and inC. fasciculatum andC. elegans of sect.Habrothamnus. Chromomycin/DAPI fluorescent double staining, sequential C-banding, and sequential silver impregnation were applied. The species differ in detail but are similar qualitatively. Four classes of heterochromatin can be discriminated. (1) CSRs, with banding properties indicating AT-rich constitutive heterochromatin. After cold-treatment CSR heterochromatin can be silver-impregnated from interphase, as chromocentres, to metaphase, as undercondensed segments. CSRs are subject to frequent heteromorphy. (2) Nucleolar organizers. Two pairs were identified in the karyotypes. Banding properties indicate GC-rich heterochromatin. The nucleolar organizing regions are less evident and their silver-reducing capability reduces during metaphase. (3) Non-nucleolar CMA-positively fluorescing bands. These are minute, polymorphic, positively C-stained, and restricted to one or a few sites in the karyotypes. (4) Indifferently fluorescing, positively C-stained bands. They occur on centromeres, some chromosome ends, and clustered over the chromosome arms. They are mostly very delicate and do not resist harsh banding treatments. — The species investigated here andC. parqui resemble each other qualitatively in heterochromatin classes (1), (2), and (3), but differ much in banding properties of class (4). Therefore, heterochromatin characteristics in the genus are not so uniform as the present results inC. strigillatum, C. fasciculatum, andC. elegans appear to show.     

Identification of a DNA sequence associated with plasmid integration in Streptomyces coelicolor A3(2)

Summary We identified a DNA element of length about 1 kb that is present in two copies in the chromosome of Streptomyces coelicolor A3(2) and is also present on the plasmid SCP1 which has been carefully defined genetically, but never isolated as extrachromosomal DNA.A copy of the element is close (within 5 kb) of a gene coding for an extracellular agarase in the chromosome of S. coelicolor A3(2) and in an NF strain, in which SCP1 has integrated into the chromosome, the agarase gene has been deleted. The element has properties reminiscent of Insertion Sequences in Escherichia coli, but it is not yet know if it can transpose.     

The human cystatin C gene (CST3), mutated in hereditary cystatin C amyloid angiopathy,is located on chromosome 20

Summary Hereditary cystatin C amyloid angiopathy has recently been shown to be caused by a point mutation in the cystatin C gene. To determine the chromosomal localization of the gene, 20 human-rodent somatic cell hybrids and a fulllength cystatin C cDNA probe were used. Southern blot analysis of BamHI digested cell hybrid DNA revealed that the probe recognizes a 10.6 kb human specific fragment and that this fragment cosegregates with human chromosome 20. Therefore, the human cystatin C gene (CST3) was assigned to chromosome 20.     

Mouse serum amyloid P-component (SAP) levels controlled by a locus on chromosome 1

Recombinant inbred strains were used to demonstrate the existence of a major locus on chromosome 1, designated Sap, which controls the endogenous concentration of the mouse acute phase reactant, serum amyloid P-component (SAP). Levels of SAP were associated with alleles at the Ly-9 locus in two sets of RI strains: BXD (C57BL/6J × DBA/2) and BXH (C57BL/6J × C3H/HeJ). Low endogenous levels of SAP were present in the C57BL/6J progenitor strain and in most of the RI strains which inherited the Ly-9 ^ballele. High levels of SAP were present in the DBA/2J and C3H/HeJ progenitors and in most of the RI strains which inherited the Ly-9 ^aallele. In the BXD strains 91% of the genetic variation of SAP levels was accounted for by segregation at the Ly-9 locus while an additional 9% was attributed to genetic factors unlinked to Ly-9. In the BXH strains the percentage of genetic variation accounted for by Ly-9 segregation was reduced to 46%, while 54% was accounted for by other genetic factors. Because of background genetic variation it was not possible to detect any crossovers between Sap and Ly-9. However, in the BXD strains the linkage between Sap and Ly-9 appears to be quite close. The B6.C-H-25 ^ccongenic strain, which carries a segment of BALB/c chromosome 1 including the minor histocompatibility locus H-25 on a C57BL/6By background, had the same endogenous SAP level as the BALB/c donor strain.     

The aryl hydrocarbon hydroxylase (Ah) locus and a novel restriction-fragment length polymorphism (RFLP) are located on mouse chromosome 12

The aryl hydrocarbon hydroxylase (Ah) locus that controls the induction of chemical carcinogen-metabolizing enzymes in mice has been found to be linked to a new restriction-fragment length polymorphism (RFLP). Only C57 BL/6 and closely related inbred strains displayed a 7.6-kbHindIII restriction fragment, while all other inbred strains tested displayed an 11.2-kbHindIII restriction fragment when using plasmid pRC2.3 as the hybridization probe. Polymorphisms in this region can also be detected with two other restriction enzymes:SacI andEcoRV. Linkage ofAh and the restriction-fragment length polymorphism was first detected using the BXD (C57BL/6 × DBA/2) recombinant inbred strains and was confirmed by a backcross. Both the restriction-fragment length polymorphism andAh were not linked to the standard genetic markersHba, Hbb, b, d, C-3, andW. However, comparison of the RFLP strain distribution pattern in the BXD recombinant inbred set with the strain distribution pattern of another RFLP, known to be located on chromosome 12, shows complete concordance in 24 of 24 strains, thereby locatingAh on chromosome 12.This research was funded in part by National Institutes of Health Grant AM31104 and by BRSG S-07RR05365-23 to J.B.W. This is contribution number 0869 from the Department of Cell and Molecular Biology.     

Synthesis of an attached autosome,C(3)RM,inDrosophila pseudoobscura

Drosophila pseudoobscura has three acrocentric autosomes. In the experiments reported, homologous arms of the third chromosome were attached to the same centromere. This is a reversed metacentric compound third chromosome, denoted by C(3)RM. This compound chromosome is relatively fertile in within-strain crosses (ca. 50% egg hatch) but sterile when outcrossed to a normal karyotype. When constructing translocations for this experiment, the behavior of the Y-autosome translocations suggested that this species can tolerate more Y chromosome deficiency while retaining fertility than canDrosophila melanogaster. Finally, there were no Robertsonian exchanges observed among the 96 autosome-autosome translocations analyzed cytologically.     

Karyotype of Callithrix mauesi (Callitrichidae,Primates) and its relations with those of C. emiliae and C. jacchus

A study was conducted on the most recently described marmoset species, Callithrix mauesi, and the results obtained were compared to those previously reported for the karyotypes of C. jacchus and C. emiliae. No mechanism of chromosome rearrangement differentiates the karyotypes of C. mauesi (2n = 44) and C. emiliae (2n = 44), which diverge from C. jacchus (2n = 46) by a Robertsonian translocation and a paracentric inversion. C. mauesi, like C. emiliae, presents telomeric constitutive heterochromatin in various chromosomes, forming large heterochromatic blocks in some. This does not occur in C. jacchus, which basically presents centromeric constitutive heterochromatin. The karyotype of C. mauesi differs from that of C. emiliae only by the amount and distribution of this telomeric constitutive heterochromatin. One of the chromosomes presenting a heterochromatic block in C. mauesi is chromosome X, a fact not previously reported in the Order Primates. The present chromosome data show that C. mauesi is closer to C. emiliae than to C. jacchus, in agreement with its inclusion in the C. argentata group. In the present paper, we describe for the first time, at the chromosome level, chimerism between fraternal twins of the same sex (XY/XY), with the heterochromatic block of pair 2 being the marker. © 1994 Wiley-Liss, Inc.     

Ribosomal protein S14 is not responsible for the Minute phenotype associated with the M(1)7C locus in Drosophila melanogaster.

Summary A locus associated with a severe Minute effect has been mapped at 7C on the X chromosome of Drosophila melanogaster. Previous work has suggested that this Minute encodes ribosomal proteins S14A and S141B. We have made a chromosomal deficiency that removes the S14 ribosomal protein genes, yet does not display the Minute phenotype. These data suggest that the S14 genes do not actually correspond to the Minute locus.     

Apoptosis Susceptibility Genes on Mouse Chromosome 9 (Rapop2) and Chromosome 3 (Rapop3)

The strain distribution pattern of susceptibility to thymocyte apoptosis induced by ionizing radiation in 20 CcS/Dem recombinant congenic (RC) strains derived from the strains BALB/cHeA (susceptible) and STS/A (resistant) indicates that this trait is controlled by several genes. Recently, we mapped a novel apoptosis susceptibility gene Rapop1 (radiation-induced apoptosis 1) to chromosome 16 (N. Mori et al., 1995, Genomics 25: 604-614). In the present study, the analysis of F2 crosses between the resistant RC strain CcS-8 and the susceptible strain BALB/cHeA or the highly susceptible RC strain CcS-10 demonstrated two additional apoptosis susceptibility genes, Rapop2 and Rapop3, located in the proximal region of chromosome 9 and the telomeric region of chromosome 3, respectively. The possible candidate genes for these loci are discussed.     

Two high linolenic mutants of Arabidopsis thaliana contain megabase-scale genome duplications encompassing the FAD3 locus

Understanding the quantitative control of fatty acid desaturation during the biosynthesis of seed storage oil has become a priority area for research, as a consequence of its importance for both human health and the substitution of mineral oil for industrial applications. We have analysed the genome structure of two mutants in Arabidopsis thaliana that show substantially elevated content of the omega‐3 polyunsaturated fatty acid linolenic acid in their seed oil. In one, rfc4, sequences totalling approximately 2 Mb from chromosome 2 have been duplicated and inserted into chromosome 3. In the other mutant, ife, chromosome 2 sequences totalling approximately 1.4 Mb have been duplicated and inserted into a linked position. In both cases, the duplications encompass the FAD3 locus, which encodes the linoleate desaturase responsible for the biosynthesis of linolenic acid for accumulation in seed storage oil. The results show that mutagens such as fast neutrons (used for the induction of rfc4) and T‐DNA (used for the induction of ife, which is not linked to the T‐DNA present in the line) can result in the duplication of very large genome segments. They also show that increasing the dosage of the FAD3‐containing genomic region results in an increase in the linolenic acid content of seed oil. Consequently, screening methods for duplication of FAD3 orthologues in oil crops may be an appropriate approach for the identification of germplasm for breeding varieties with increased proportions of linolenic acid in the oil that they produce.     

Chalcone synthase in rice (Oryza sativa L.): Detection of the CHS protein in seedlings and molecular mapping of the chs locus

The chalcone synthase is a key enzyme that catalyses the first dedicated reaction of the flavonoid pathway in higher plants. The chs gene and its protein product in rice has been investigated. The presence of a chalcone synthase (CHS) protein in rice seedlings and its developmental stage-specific expression has been demonstrated by western analysis. The chalcone synthase of rice was found to be immunologically similar to that of maize. A rice cDNA clone, Os-chs cDNA, encoding chalcone synthase, isolated from a leaf cDNA library of an indica rice variety Purpleputtu has been mapped to the centromeric region of chromosome 11 of rice. It was mapped between RFLP markers RG2 and RG103. RG2 is the nearest RFLP marker located at a genetic distance of 3.3 cM. Some segments of chromosome 11 of rice including chs locus are conserved on chromosome 4 of maize. The markers, including chs locus on chromosome 11 of rice are located, though not in the same order, on chromosome 4 of maize. Genetic analysis of purple pigmentation in two rice lines, Abhaya and Shyamala, used in the present mapping studies, indicated the involvement of three genes, one of which has been identified as a dominant inhibitor of leaf pigmentation. The Os-chs cDNA shows extensive sequence homology, both for DNA and protein (deduced), to that of maize, barley and also to different monocots and dicots.     

Histidine decarboxylase phenotypes of inbred mouse strains: A regulatory locus (Hdc) determines kidney enzyme concentration

Mouse kidney histidine decarboxylase (HDC) provides a model system to study genetic control of a hormone-regulated enzyme (inducible by estrogen and thyroxine; repressible by testosterone). Five major HDC phenotypes scored on the basis of (i) enzyme activity and (ii) the difference in activity between the sexes (females usually higher than males) have been discovered by screening 38 strains of mice. One genetic difference between high-activity strains (DBA/2 and C3H/He) and low-activity strains (C57BL/6 and C57BL/10) has been examined in detail. The phenotypic difference segregates as a single gene in both conventional crosses and between recombinant inbred (RI) strains. Immunoprecipitation has shown that the activity difference is due to an alteration in the number of enzyme molecules. The phenotypic difference between high and low strains can therefore be attributed to different alleles of a single regulatory locus, Hdc; the alleleHdc ^d determines low HDC concentration, and the allele Hdc ^d high concentration. Hdc has been mapped to chromosome 2 using data from both comparisons of strain distribution patterns of previously mapped loci within RI strains and a conventional three-point cross. The probable gene order is B2m-pa-Hdc, with map distances of 3.1±1.7 and 2.0±1.4 cM, respectively.This work was supported by an MRC project grant to Grahame Bulfield, an SERC research studentship to S. A. M. Martin, and NIH Research Grant GM 18684 from the National Institute of General Medical Sciences to B. A. Taylor. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory animal care.     

Characterization of Bglu3, a mouse fasting glucose locus, and identification of Apcs as an underlying candidate gene

Bglu3 is a quantitative trait locus for fasting glucose on distal chromosome 1 identified in an intercross between C57BL/6 (B6) and C3H/HeJ (C3H) apolipoprotein E-deficient (apoE(-/-)) mice. This locus was subsequently replicated in two separate mouse intercrosses. The objective of this study was to characterize Bglu3 through construction and analysis of a congenic strain and identify underlying candidate genes. Congenic mice were constructed by introgressing a genomic region harboring Bglu3 from C3H.apoE(-/-) into B6.apoE(-/-) mice. Mice were started with a Western diet at 6 wk of age and maintained on the diet for 12 wk. Gene expression in the liver was analyzed by microarrays. Congenic mice had significantly higher fasting glucose levels and developed more significant glucose intolerance compared with B6.apoE(-/-) mice on the Western diet. Microarray analysis revealed 336 genes to be differentially expressed in the liver of congenic mice. Further pathway analysis suggested a role for acute phase response signaling in regulating glucose intolerance. Apcs, encoding an acute phase response protein serum amyloid P (SAP), is located underneath the linkage peak of Bglu3. Multiple single nucleotide polymorphisms between B6 and C3H mice were detected within and surrounding Apcs. Apcs expression in the liver was significantly higher in congenic and C3H mice compared with B6 mice. The Western diet consumption led to a gradual rise in plasma SAP levels, which was accompanied by rising fasting glucose in both B6 and C3H apoE(-/-) mice. Expression of C3H Apcs in B6.apoE(-/-) mice aggravated glucose intolerance. Bglu3 is confirmed to be a locus affecting diabetes susceptibility, and Apcs is a probable candidate gene.     

Autosomal dominant retinitis pigmentosa: a new multi-allelic marker (D3S621) genetically linked to the disease locus (RP4)

Summary We report the characterization of a new eightallele microsatellite (D3S621) isolated from a human chromosome 3 library. Two-point and multi-locus genetic linkage analysis have shown D3S621 to co-segregate with the previously mapped RP4 ( _m=0.12, Z _m=4.34) and with other genetic markers on the long arm of the chromosome, including D3S14 (R208) ( _m=0.00, Z _m= 15.10), D3S47 (C17) ( _m=0.11, Z _m=4.95), Rho ( _m= 0.07, Z _m=1.37), D3S21 (L182) ( _m=0.07, Z _m=2.40) and D3S19 (U1) ( _m=0.13, Z _m=2.78). This highly informative marker, with a polymorphic information content of 0.78, should be of considerable value in the extension of linkage data for autosomal dominant retinitis pigmentosa with respect to locii on the long arm of chromosome 3.     

A null mutation at the mouse Phosphoglucomutase-1 locus and a new locus,Pgm-3

A null mutation at the phosphoglucomutase locus (Pgm-1) was discovered by electrophoretic analysis of the inbred mouse strain C57 BL/6J. The null allele (Pgm-1 ⁿ) was shown to segregate as a Mendelian unit alternative to the Pgm-1 ^a and Pgm-1 ^b alleles. Mice expressing the Pgm-1 ⁿ allele, either in the heterozygous or homozygous state, are viable, healthy, and fertile. The occurrence of the Pgm-1 ⁿ mutant revealed a previously unreported genetic locus (Pgm-3) that controls the expression of a third phosphoglucomutase. Two electrophoretically expressed alleles of Pgm-3 (inherited without dominance) are found in the inbred mouse strains C57 BL/6J and DBA/2J. Linkage observed between the Pgm-3 locus, the dilute locus (d) and the cytoplasmic malic enzyme locus (Mod-1) has allowed assignment of the Pgm-3 locus to chromosome 9. A striking tissue specific expression of Pgm-1 and Pgm-3 was observed. Products of the Pgm-3 locus were detected in kidney, testes, brain, and heart. In contrast, Pgm-1 controlled isozymes were present in kidney, spleen, ovaries, and erythrocytes.Financial support for this work was provided in part by Contract #263-78-C-0393 from the National Institute of Environmental Health Sciences to the Research Triangle Institute.