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.     

Mapping genetic loci that regulate lipid levels in a NZB/B1NJxRF/J intercross and a combined intercross involving NZB/B1NJ, RF/J, MRL/MpJ, and SJL/J mouse strains

The NZB/B1NJ (NZB) mouse strain exhibits high cholesterol and HDL levels in blood compared with several other strains of mice. To study the genetic regulation of blood lipid levels, we performed a genome-wide linkage analysis in 542 chow-fed F2 female mice from an NZBxRF/J (RF) intercross and in a combined data set that included NZBxRF and MRL/MpJxSJL/J intercrosses. In the NZBxRF F2 mice, the cholesterol and HDL concentrations were influenced by quantitative trait loci (QTL) on chromosome (Chr) 5 [logarithm of odds (LOD) 17-19; D5Mit10] that was in the region identified earlier in crosses involving NZB mice, but two QTLs on Chr 12 (LOD 4.7; D12Mit182) and Chr 19 (LOD 5.7; D19Mit1) were specific to the NZBxRF intercross. Triglyceride levels were affected by two novel QTLs at D12Mit182 (LOD 8.7) and D15Mit13 (LOD 3.5). The combined-cross linkage analysis (1,054 mice, 231 markers) 1) identified four shared QTLs (Chrs 5, 7, 14, and 17) that were not detected in one of the parental crosses and 2) improved the resolution of two shared QTLs. In summary, we report additional loci regulating lipid levels in NZB mice that had not been identified earlier in crosses involving the NZB strain of mice. The identification of shared loci from multiple crosses increases confidence toward finding the QTL gene.     

Mapping of the Mod-1 locus on mouse Chromosome 9

A new method for typing the Mod-1 locus on mouse Chromosome (Chr) 9 was developed, based on restriction fragment length polymorphism (RFLP) within a polymerase chain reaction (PCR)-amplified fragment. The new method led us to revise the strain distribution pattern (SDP) of Mod-1 in the BXD (C57BL/6JxDBA/2J) and AKXD (AKR/J x DBA/2J) recombinant inbred (RI) strains. The new SDP eliminates several previously reported examples of double recombination events between Mod-1 and the closest flanking loci in the BXD and AKXD strains. In the BXD strains, the revised SDP of Mod-1 was identical to that of the Mod-1-related D9Rtil locus. Thus, the identity of D9Rtil as a Mod-1-related locus rather than Mod-1 itself is in question. The method was also applied to an interspecific backcross panel between an inbred strain of Mus musculus molossinus (MSM/Ms) and C57BL/6J to map Mod-1 with respect to surrounding microsatellite loci, defining the proximal localization of Mod-1 with respect to D9Mit10 with a genetic distance of 0.6±0.6 cM.     

A major determinant quantitative-trait locus responsible for atopic dermatitis-like skin lesions in NC/Nga mice is located on Chromosome 9

NC/Nga (NC) is a newly discovered model mouse for human atopic dermatitis, NC mice showing specific symptoms such as dermatitis and overproduction of IgE. To detect the loci responsible for the onset of dermatitis in the mice, backcross (N2) progeny between (NCxMSM/MS)F1 and NC were generated, where MSM/MS is an inbred strain from Japanese wild mice, Mus musculus molossinus. Linkage disequilibrium between dermatitis and various chromosome-specific microsatellite markers was then examined in the N2 segregants with severe dermatitis. The analysis revealed that the locus of the major determinant (designated here as derm1) was tightly linked to D9Mit163, D9Mit72, D9Mit143, D9Mit103, D9Mit207, and D9Mit209, because these markers showed the highest and most significant chi2 values. Since no recombination was observed among the markers in our linkage map, a radiation hybrid (RH) panel was applied to locate the derm1 locus more precisely. The markers were separated on the RH map, and their order was D9Mit163-D9Mit72-D9Mit143-D9Mit103-D9Mit207-D9Mit209 from the centromere. Several functional candidate genes are located near the locus derm1. These candidates are Thy1, Cd3d, Cd3e, Cd3g, Il10ra, 1118, and Csk, all of which could be involved in allergic responses through effects on T-cell function. Of these candidates, Csk is the strongest for NC dermatitis, since its map position was most tightly linked to the derm1 locus.     

Mapping tissue-specific genes correlated with age-dependent changes in protein stability and function

Biophysical measurements indicative of protein stability and function were performed on crude extracts from liver, muscle, and lens of a genetically heterogeneous mouse population. Genetic information was used to search for quantitative trait loci (QTL) that influenced the biophysical traits, with emphasis on phenotypes that previously have been shown to be altered in aged animals. Spectroscopic and enzymatic assays of crude liver and muscle tissue extracts from approximately 600 18-month-old mice, the progeny of (BALB/cJxC57BL/6J)F1 females and (C3H/HeJxDBA/2J)F1 males, were used to measure the susceptibility of a ubiquitous glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), to thermal denaturation. The rate constant for thermal inactivation of GAPDH correlated with markers on chromosome 5 (D5Mit79 and D5Mit251) for muscle lysates and chromosome 15 (D15Mit63 and D15Mit100) for liver tissue. The degree of variability of inactivation rate constants, a measure of the heterogeneity of muscle GAPDH in tissue extracts, was also associated with markers on chromosome 5 (D5Mit79 and D5Mit205). In addition, spectroscopic characteristics of extracted eye lens proteins were evaluated for their susceptibility to photooxidative stress. Absorbance and fluorescence emission characteristics of the lens proteins were mapped to QTL on chromosomes 5 and 15 (D5Mit25 and D15Mit171) while the degree of heterogeneity in photochemical oxidation kinetics was associated with a marker on the chromosome 8 (D8Mit42). Recent work has shown that GAPDH possesses a number of non-glycolytic functions including DNA/RNA binding and regulation of protein expression. Tissue specific differences in GAPDH stability may have significant consequences to these alternate functions during aging.     

Fractioned DNA pooling: a new cost-effective strategy for fine mapping of quantitative trait loci

Selective DNA pooling (SDP) is a cost-effective means for an initial scan for linkage between marker and quantitative trait loci (QTL) in suitable populations. The method is based on scoring marker allele frequencies in DNA pools from the tails of the population trait distribution. Various analytical approaches have been proposed for QTL detection using data on multiple families with SDP analysis. This article presents a new experimental procedure, fractioned-pool design (FPD), aimed to increase the reliability of SDP mapping results, by "fractioning" the tails of the population distribution into independent subpools. FPD is a conceptual and structural modification of SDP that allows for the first time the use of permutation tests for QTL detection rather than relying on presumed asymptotic distributions of the test statistics. For situations of family and cross mapping design we propose a spectrum of new tools for QTL mapping in FPD that were previously possible only with individual genotyping. These include: joint analysis of multiple families and multiple markers across a chromosome, even when the marker loci are only partly shared among families; detection of families segregating (heterozygous) for the QTL; estimation of confidence intervals for the QTL position; and analysis of multiple-linked QTL. These new advantages are of special importance for pooling analysis with SNP chips. Combining SNP microarray analysis with DNA pooling can dramatically reduce the cost of screening large numbers of SNPs on large samples, making chip technology readily applicable for genomewide association mapping in humans and farm animals. This extension, however, will require additional, nontrivial, development of FPD analytical tools.     

Low resolution mapping around the flavivirus resistance locus (Flv) on mouse Chromosome 5

Although the phenomenon of innate resistance to flaviviruses in mice was recognized many years ago, it was only recently that the genetic locus (Flv) controlling this resistance was mapped to mouse Chromosome (Chr) 5. Here we report the fine mapping of the Flv locus, using 12 microsatellite markers which have recently been developed for mouse Chr 5. The new markers were genotyped in 325 backcross mice of both (C3H/HeJxC3H/ RV)F₁xC3H/HeJ and (BALB/cxC3H/RV)F₁xBALB/c backgrounds, relative to Flv. The composite genetic map that has been constructed identifies three novel microsatellite loci, D5Mit68, D5Mit159, and D5Mit242, tightly linked to the Flv locus. One of those loci, D5Mit159, showed no recombinations with Flv in any of the backcross mice analyzed, indicating tight linkage (<0.3 cM). The other two, D5Mit68 and D5Mit242, exhibited two and one recombinations with Flv (0.6 and 0.3 cM) respectively, defining the proximal and distal boundaries of a 0.9-cM segment around this locus. The proximal flanking marker, D5Mit68, maps to a segment on mouse Chr 5 homologous to human Chr 4. This, together with the previous data produced by our group, locates Flv to a region on mouse Chr 5 carrying segments that are conserved on either human Chr 4, 12, or 7, but present knowledge does not allow precise identification of the syntenic element.     

Mapping genes that control hormone-induced ovulation rate in mice.

The present study mapped quantitative trait loci (QTL) that control 6-fold genetic differences in hormone-induced ovulation rate (HIOR) between C57BL/6J (B6) (HIOR = 54) and A/J strain mice (HIOR = 9). (The gene name is Ovulation Rate Induced [ORI] QTL and the gene symbol is Oriq.) QTL linkage analysis was conducted on 167 (B6xA)xA backcross mice at 165 loci. Suggestive B6 ORI QTL that control the number of eggs in cumulus mapped, as follows, near: Cyp19 and D9Mit4 on chromosome (Chr) 9 (Oriq1); D2Mit433 on Chr2 (Oriq2); D6Mit316 on Chr6 (Oriq3); DXMit22 on ChrX (Oriq4) and were associated with a 2.7, 2.7, 2.6, and 4.2 egg increases in HIOR, respectively. Oriq3 was significant (LOD = 3.45) based on composite interval mapping. QTL linkage analysis of the number of eggs matured by endogenous gonadotropins and ovulated by eCG mapped a significant Oriq5 to Chr 10 and suggestive Oriq to Chr 6, 7, and X. These data provide the first molecular genetic markers for reproductive QTL that control major differences in ovarian responsiveness to gonadotropins. These and closely linked syntenic molecular markers will enable a more accurate prediction of ovarian responsiveness to gonadotropins and provide selection criteria for improving reproductive performance in diverse mammalian species.     

Genetic analysis of alcohol intake in recombinant inbred and congenic strains derived from A/J and C57BL/6J progenitors

The objective of the present study was to map quantitative trait loci (QTL) for alcohol intake using A × B/B × A recombinant inbred (RI) and AcB/BcA recombinant congenic (RC) strains of mice that were independently derived from the A/J and C57BL/6J progenitors. Mice were screened for levels of alcohol consumption with four days of forced exposure to alcohol, followed by three weeks of free choice between water and a 10% alcohol solution. Alcohol consumption data previously collected for 27 A × B/B × A RI strains were reanalyzed using a larger marker set and composite interval mapping. The reanalysis found markers on Chromosome 2 (D2Mit74, 107 cM) (males and females) and on Chromosome 11 (Pmv22, 8 cM) (females only) that exceeded the threshold for significant loci, and found suggestive loci (in males) on Chromosomes 10 (D10 Mit126, 21 cM), 12 (D12Mit37, 1 cM), 15 (Pdgfb, 46.8 cM), and 16 (D16Mit125, 29 cM). An additional suggestive locus was identified in female RI mice on Chromosome 11 (D11Mit120, 47.5 cM). Composite interval mapping (CIM) analysis indicated that there was a significant association between loci at Pdgfb and D2Mit74 in both males and females. Analysis of the AcB/BcA RC strains identified 11 QTL on Chromosomes 2, 3, 5,6, 7, 8, 9, 10, 12, 13, and 15. QTL on Chromosomes 7, 10, 12, and 15 were identified in both the A × B/B × A RI and AcB/BcA RC strains of mice. Additional QTLs identified on Chromosomes 2, 3, 7, 11, and 15 overlap with those previously identified in the literature using strains of mice with a C57BL/6J progenitor.     

The positions of 12 simple sequence repeat markers relative to reference loci on mouse Chromosome 16

The genetic map positions of 12 simple sequence repeat (SSR) markers spanning mouse Chromosome (Chr) 16 were determined relative to reference markers on that chromosome. Interval mapping data were obtained with a panel of DNAs from two intersubspecific backcrosses. All but one of the markers were typed by use of nonradioactive polymerase chain reaction (PCR) products analyzed on agarose gels. The marker order was determined to be Prm-1, D16Mit9, Igl-1, D16Mit29, D16Mit1/D16Mit2, Smst, D16Mit4, D16Mit11, Gap43, D16Mit14, D16Mit30, D16Mit5, Pit-1, D16Mit27, D16H21S16 (formerly D21S16h), D16Mit19, App, D16Mit7, Sod-1. Two of these markers mapped to the known human Chr 21 (HSA21)/Chr 16 conserved linkage group. Nine additional SSR markers could not be typed because they were not polymorophic (four markers), did not amplify MOLD/Rk DNA (three markers), or failed to give PCR products under a range of conditions (two markers). A subset of the most robust SSRs provide a useful marker set for the analysis of previously unmapped crosses.     

Genetic regulation of lipopolysaccharide-induced interleukin 1 production by murine peritoneal macrophages

The production of IL 1 by LPS-stimulated peritoneal macrophages from inbred mouse strains was studied. Macrophages from A/J (A) mice were deficient in IL 1 production, when compared with high IL 1-producing strains, including C57BL/6J (B). The difference between A and B macrophages was maintained over a wide LPS concentration range and throughout a 72-hr incubation period. Because of these differences, it was possible to investigate the mechanisms regulating IL 1 production by applying techniques of genetic analysis by using recombinant inbred (RI) strains derived from the A and B progenitors. A strain distribution pattern (SDP) of IL 1 production (low/high response) was obtained with the use of 15 AXB/BXA RI strains. This suggested the presence of a major gene locus controlling the production of IL 1 in response to LPS stimulation, with allelic differences presumably resulting in deficient or efficient IL 1 production. In addition, there appeared to be one or more other loci involved in determining the magnitude of the IL 1 response to LPS in the responder mice. The IL 1 response did not appear to be linked to the major histocompatibility complex, since B10.A mice (which share the same H-2a haplotype as A/J) were efficient IL 1 producers. There did not appear to be any correlation between the degree of IL 1 production and the magnitude of the peritoneal macrophage inflammatory response, or between IL 1 production and LPS responsiveness (as determined by splenocyte proliferation). SDP analysis also indicated that the IL 1 response was not linked to macrophage tumoricidal activity. A comparison of the SDP for IL 1 production with a library of SDP for other known genetic waits suggested linkage with at least four loci on chromosome 1.     

Identification of quantitative trait loci that regulate obesity and serum lipid levels in MRL/MpJ x SJL/J inbred mice

The total body fat mass and serum concentration of total cholesterol, HDL cholesterol, and triglyceride (TG) differ between standard diet-fed female inbred mouse strains MRL/MpJ (MRL) and SJL/J (SJL) by 38-120% (P < 0.01). To investigate genetic regulation of obesity and serum lipid levels, we performed a genome-wide linkage analysis in 621 MRLx SJL F2 female mice. Fat mass was affected by two significant loci, D11Mit36 [43.7 cM, logarithm of the odds ratio (LOD) 11.2] and D16Mit51 (50.3 cM, LOD 3.9), and one suggestive locus at D7Mit44 (50 cM, LOD 2.4). TG levels were affected by two novel loci at D1Mit43 (76 cM, LOD 3.8) and D12Mit201 (26 cM, LOD 4.1), and two suggestive loci on chromosomes 5 and 17. HDL and cholesterol concentrations were influenced by significant loci on chromosomes 1, 3, 5, 7, and 17 that were in the regions identified earlier for other strains of mice, except for a suggestive locus on chromosome 14 that was specific to the MRL x SJL cross. In summary, linkage analysis in MRL x SJL F2 mice disclosed novel loci affecting TG, HDL, and fat mass, a measure of obesity. Knowledge of the genes in these quantitative trait loci will enhance our understanding of obesity and lipid metabolism.     

Molecular markers near two mouse Chromosome 13 genes,muted and pearl,which cause platelet storage pool deficiency (SPD)

The recessive muted (mu) and pearl (pe) mutations on Chromosome (Chr) 13 cause pigment dilution and platelet storage pool deficiency (SPD) in mice. In addition, mu causes inner ear abnormalities and pe has symptoms associated with night blindness. Using an interspecific backcross involving the wild-derived Mus musculus musculus (PWK) stock, we have mapped 33 microsatellite markers and four cDNAs relative to mu, pe, and another recessive mutation, satin (sa). Analyzing a total of 528 backcross offspring, we found tight linkage between the pigment loci and several microsatellite markers (D13Mit87, D13Mit88, D13Mit137 with mu; and D13Mit104, D13Mit160, D13Mit161, and D13Mit169 with pe). These markers should aid the eventual molecular identification of these specific SPD genes.     

小鼠15号染色体上脊髓重数量性状基因座的精细定位

目的以前的研究结果表明,控制小鼠脊髓重的一个数量性状基因座(QTL)位于15号染色体D15Mit158附近,跨度约30cM。为分离和确认脊髓重相关基因,本文对该QTL区域进行了精细定位。方法以高级互交系小鼠A/J×C57BL/6J(F4)为研究对象,选择脊髓重偏向两极的个体,在D15Mit158位点附近作高密度局部基因组扫描,用Map Manager QTX19软件对脊髓重与基因型进行连锁不平衡分析。结果在15号染色体D15Mit107附近出现了一个很强的连锁峰,LRS值为17.3(P=1.8×10-4),变异解释率为27%,LOD值达到3.75,可以认定为一主效QTL。该QTL跨度范围为3.2cM。另一个提示可能具有连锁关系的QTL位点在D15Mit28附近,LRS值为7.6(P=0.02),变异解释率为13%,跨度范围为5.0cM。结论控制小鼠脊髓重的D15Mit158区域实际上含有两个QTL,其中一个主效QTL位于15号染色体上宽约3.2cM的D15Mit107位点附近;另一个可能的QTL位于宽约5.0cM的D15Mit28附近。     

Concordance of murine quantitative trait loci for salt-induced hypertension with rat and human loci

To investigate the genetic control of salt-induced hypertension, we performed a quantitative trait locus analysis on male mice from a reciprocal backcross between the salt-sensitive C57BL/6J and the normotensive A/J inbred mouse strains after they were provided with water containing 1% salt for 2 weeks. Genome-wide scans performed on these mice and analyzed with a combination of conventional marker-based regressions and a novel simultaneous search for pairs revealed six significant quantitative trait loci associated with salt-induced blood pressure, two of which were interacting loci. These six loci, named Bpq1-6 for blood pressure quantitative trait loci, mapped to D1Mit334, D1Mit14, D4Mit164, D5Mit31, D6Mit15, and D15Mit13. Furthermore, five of these six loci were concordant with hypertension loci in rats, and four were concordant with hypertension loci in humans, suggesting that quantitative trait loci mapping in model organisms can be used to guide the search for human blood pressure genes.     

A Radiation Hybrid Map of Mouse Chromosome 13

A mouse radiation hybrid (RH) panel was used to make a framework map for the entire length of mouse chromosome (Chr) 13. Forty-one loci were typed, and while most used primers flanking simple sequence repeats, some genes were included. The most proximal and distal loci are D13Mit132 and D13Mit35. The estimate of map length for Chr 13 is 1328 cR. The map is compared with the same set of loci from the consensus map for Chr 13, which is 70 cM in length, and also with a recombinational map derived from an intraspecies cross typed for many of the same loci. The mouse RH panel gave good resolution for Chr 13 and at the distal end allowed separation of previously nonrecombinant markers that are present on a single 620-kb YAC clone. Data analysis was performed using the RH option for Map Manager QT. This framework RH map of Chr 13 is the second of a series of RH maps for mouse chromosomes.     

Analysis of microsatellite polymorphism in inbred knockout mice

Previously, we found that the genotype of 42 out of 198 mouse microsatellite loci, which are distributed among all chromosomes except the Y chromosome, changed from monomorphism to polymorphism (CMP) in a genetically modified inbred mouse strain. In this study, we further examined whether CMP also relates to the homologous recombination in gene knockout (KO) mouse strains. The same 42 microsatellite loci were analyzed by polymerase chain reaction (PCR) in 29 KO inbred mouse strains via short tandem sequence repeat (STR) scanning and direct sequence cloning to justify microsatellite polymorphisms. The C57BL/6J and 129 mouse strains, from which these 29 KO mice were derived, were chosen as the background controls. The results indicated that 10 out of 42 (23.8%) loci showed CMP in some of these mouse strains. Except for the trinucleotide repeat locus of D3Mit22, which had microsatellite CMP in strain number 9, the core sequences of the remaining 41 loci were dinucleotide repeats, and 9 out of 41 (21.95%) showed CMPs among detected mouse strains. However, 11 out of 29 (37.9%) KO mice strains were recognized as having CMPs. The popular dinucleotide motifs in CMP were (TG)(n) (50%, 2/4), followed by (GT)(n) (27.27%, 3/11) and (CA)(n) (23.08%, 3/13). The microsatellite CMP in (CT)(n) and (AG)(n) repeats were 20% (1/5). According to cloning sequencing results, 6 KO mouse strains showed insertions of nucleotides whereas 1 showed a deletion. Furthermore, 2 loci (D13Mit3 and D14Mit102) revealed CMP in 2 strains, and mouse strain number 9 showed CMPs in two loci (D3Mit22 and D13Mit3) simultaneously. Collectively, these results indicated that microsatellite polymorphisms were present in the examined inbred KO mice.     

High-resolution linkage map in the vicinity of the Lp locus

Looptail (Lp) is a mutation that profoundly affects neurulation in mouse and is characterized by craniorachischisis, an open neural tube extending from the midbrain to the tail in embryos homozygous for the mutation. Lp maps to the distal portion of mouse chromosome 1, and as part of a positional cloning approach, we have generated a high-resolution linkage map of the Lp chromosomal region. For this, we have carried out extensive segregation analysis in a total of 706 backcross mice informative for Lp and derived from two crosses, (Lp/ + X SJL/J)F1 X SJL/J and (Lp/ + X SWR/J)F1 X SWR/J. In addition, 269 mice from a (Mus spretus X C57BL/6J)F1 X C57BL/6J interspecific backcross were also used to order marker loci and calculate intergene distances for this region. With these mice, a total of 28 DNA markers corresponding to either cloned genes or anonymous markers of the SSLP or SSCP-types were mapped within a 5-cM interval overlapping the Lp region, with the following locus order and interlocus distances (in cM): centromere-D1Mit110 / Atp1β1 / Cd3ζ / Cd3η / D1Mit145 — D1Hun14 / D1Mit15 — D1Mit111 / D1Mit112 — D1Mit114 — D1Mit148 / D1Mit205/ D1Mit36 / D1Mit146 / D1Mit147 / D1Mit270 / D1Hun13 — Fcgr2 — Mpp — Apoa2/Fcer1γ - Lp - D1Mit149 / Spna1/Fcer1α-Eph1-Hlx1/D1Mit62. These studies have allowed the delineation of a maximum genetic interval for Lp of 0.5 cM, a size amenable to physical mapping techniques.     

用微卫星标记技术对国内BALB/c小鼠遗传质量的分析

为了解和掌握国内BALB/c小鼠遗传质量状况,验证微卫星标记技术在近交系小鼠遗传检测中应用的可靠性,应用所筛选的小鼠不同染色体上的14个微卫星基因座,通过PCR扩增对北京、上海、沈阳、广州、长春、重庆和哈尔滨7个地区11个厂家提供的BALB/c小鼠进行遗传质量分析.结果北京、上海、哈尔滨及广州地区7家BALB/c小鼠在14个基因座均呈现一条清晰条带,且群体间呈单态性.沈阳、广州、长春和重庆4个群体有8个基因座在群体内表现杂合或呈多态性;其中沈阳和长春分别在1个基因座上表现多态性和杂合;广州另一群体有4个基因座出现杂合或多态性;重庆群体有7个基因座表现为杂合或多态性,在D10Mit180基因座与上海群体比较呈现多态性.     

Assignment of a locus for mouse lung tumor susceptibility to proximal Chromosome 19

Previous studies have hypothesized that at least three genetic loci contribute to differences in pulmonary adenoma susceptibility between mouse strains A/J and C57BL/6J. One gene that may confer susceptibility to lung tumorigenesis is the Kras protooncogene. To identify other relevant loci involved in this polygenic trait, we determined tumor multiplicity in 56 randomly chosen N-ethyl-N-nitrosourea-treated (A/J×C57BL/6J) N1×C57BL/6 backcross (AB6N2) progeny and correlated it with genotypes at 77 microsatellite markers spanning the genome. A correlation of lung tumor multiplicity phenotypes with genotypes of microsatellite markers on distal Chromosome (Chr) 6 in the Kras region (Pas1) was confirmed, and a new region on Chr 19 (designated Pas3) was identified that also contributes to susceptibility. Linkage analysis on Chr 19 with 270 AB6N2 mice localized the region flanked by D19Mit42 and D19Mit19 that is most closely associated with lung tumor susceptibility. The Pas3 locus may be an enhancer of the susceptibility locus on Chr 6.