In this study, we reported the repaid construction of a molecular marker linkage map of rice (Oryza sativa L.). An F-2 population from the cross between Annong S-1 and Nanjing 11 was used to construct a genetic linkag...In this study, we reported the repaid construction of a molecular marker linkage map of rice (Oryza sativa L.). An F-2 population from the cross between Annong S-1 and Nanjing 11 was used to construct a genetic linkage map of rice. Total of 142 newly screened AFLP markers and 30 anchor markers (25 SSR markers and 5 RFLP markers) were mapped on the 12 chromosomes covering 1537.4 cM of rice genome. The average interval between these markers was 9.0 cM. The total work which usually was finished in more than one year was finished within only 3 months by one person. This is the first plant AFLP map developed in China. A new thermosensitive genic male sterile gene in rice, tms5, was Egged and mapped onto chromosome 2 during the development of the linkage map.展开更多
Modeling linkage disequilibria (LD) between genes usually observed in admixed natural populations has been shown an effective approach in high-resolution mapping of disease genes in humans. A prerequisite to obtain ac...Modeling linkage disequilibria (LD) between genes usually observed in admixed natural populations has been shown an effective approach in high-resolution mapping of disease genes in humans. A prerequisite to obtain accurate estimation of recombination fraction between genesat a marker locus and the disease locus using the approach is a reliable prediction of the proportion of the admixture populations. The present study suggested the use of gene frequencies to predict the estimate of the admixture proportion based on the observation that the gene frequencies are much more stable quantities than the haplotype frequencies over evolution of the population. In this paper, we advanced the theory and methods by which the decay rate of nonlinear term of LD in admixed population may be used to estimate the recombination fraction between the genes. Theoretical analysis and simulation study indicate that, the larger the difference of gene frequencies between parental populations and the more closely the展开更多
Insufficient available phosphorus in soil has become an important limiting factor for the improvement of yield and quality in soybean. The mining of QTLs and candidate genes controlling soybean phosphorus utilization ...Insufficient available phosphorus in soil has become an important limiting factor for the improvement of yield and quality in soybean. The mining of QTLs and candidate genes controlling soybean phosphorus utilization related traits is a necessary strategy to solve this problem. In this study, 11 phosphorus utilization related traits of a natural population of 281 typical soybean germplasms and a recombinant inbred line(RIL) population of 270 lines were evaluated under different phosphorus conditions at two critical stages: the four-leaf stage as the seedling critical stage was designated as the Tstage, and the six-leaf stage as the flowering critical stage was designated as the Tstage. In total, 200 single nucleotide polymorphism(SNP) loci associated with phosphorus utilization related traits were identified in the natural population, including 91 detected at the Tstage, and 109 detected at the Tstage. Among these SNP loci, one SNP cluster(s715611375, ss715611377, ss715611379 and ss715611380) on Gm12 was shown to be significantly associated with plant height under the low phosphorus condition at the Tstage, and the elite haplotype showed significantly greater plant height than the others. Meanwhile, one pleiotropic SNP cluster(ss715606501, ss715606506 and ss715606543) on Gm10 was found to be significantly associated with the ratio of root/shoot, root and total dry weights under the low phosphorus condition at the Tstage, and the elite haplotype also presented significantly higher values for related characteristics under the phosphorus starvation condition. Furthermore, four co-associated SNP loci(ss715597964, ss715607012, ss715622173 and ss715602331) were identified under the low phosphorus condition at both the Tand Tstages, and 12 QTLs were found to be consistent with these genetic loci in the RIL population. More importantly, 14 candidate genes, including MYB transcription factor, purple acid phosphatase, sugar transporter and HSP20-like chaperones superfamily genes, etc., showed differential expression levels after low phosphorus treatment, and three of them were further verified by q RT-PCR. Thus, these genetic loci and candidate genes could be applied in markerassisted selection or map-based gene cloning for the genetic improvement of soybean phosphorus utilization.展开更多
Resistance to whitebacked planthopper(WBPH)in Chinese japonica riceChunjiang 06(CJ-06)was mediated by sucking inhibitory and ovicidal mecha-nism.The ovicidal reponse was a common self-defense mechanism againstWBPH in ...Resistance to whitebacked planthopper(WBPH)in Chinese japonica riceChunjiang 06(CJ-06)was mediated by sucking inhibitory and ovicidal mecha-nism.The ovicidal reponse was a common self-defense mechanism againstWBPH in japonica.The ovicidal gene and its chromosomal position had alreadybeen identified.The sucking inhibitory nature of CJ-06 caused a definenon-preference behavior of WBPH in fields.A single dominant gene governed展开更多
Congenital microphthalmia is a developmental ocular disorder and might be caused by the mutations in the genes involved in eye development. To uncover the genetic cause in a six-generation Chinese pedigree with autoso...Congenital microphthalmia is a developmental ocular disorder and might be caused by the mutations in the genes involved in eye development. To uncover the genetic cause in a six-generation Chinese pedigree with autosomal dominant congenital microphthalmia, we performed genescan and linkage analysis in this family. Fourteen microsatellite markers on chromosomes 3, 11, 14 and 15 were selected as genetic markers according to the five pre-viously reported loci associated with microphthalmia (MITF, SOX2, PAX6, MCOP and NNO2). The genomic DNA of each member in the pedigree was amplified with 14 pairs of fluorescence labeled primers. Genome screening and genotyping were conducted on ABI377 DNA sequencer and linkage analysis was performed with Linkage software package. All two-point LOD scores of linkage analysis between the suggested disease genes and microsatellite markers were <-2, which indicated that none of the five genes were responsible for microphthalmia in this Chinese family. Microphthalmia in this family may be caused by mutation in a new gene which is essential in eye development.展开更多
Bruchid beetle(Callosobruchus chinensis) poses a serious threat to the production and storage of mung bean(Vigna radiata). Mapping bruchid resistance(Br) will provide an important basis for cloning the responsible gen...Bruchid beetle(Callosobruchus chinensis) poses a serious threat to the production and storage of mung bean(Vigna radiata). Mapping bruchid resistance(Br) will provide an important basis for cloning the responsible gene(s) and elucidating its functional mechanism, and will also facilitate marker-assisted selection in mung bean breeding. Here, we report the construction of the genetic linkage groups of mung bean and mapping of the Br1 locus using an RIL population derived from a cross between Berken, a bruchid-susceptible line, and ACC41, a bruchid-resistant line. A total of 560 markers were mapped onto 11 linkage groups,with 38.0% of the markers showing distorted segregation. The lengths of the linkage groups ranged from 45.2 to 117.0 c M with a total coverage of 732.9 c M and an average interval of1.3 c M between loci. Br1 was located on LG9 between BM202(0.7 c M) and Vr2-627(1.7 c M).Based on 270 shared SSR markers, most of the linkage groups were assigned to specific chromosomes. These results should further accelerate the genetic study of this crop.展开更多
Poplars are among the most important deciduous tree species in China. China is replete with natural resources of poplars. Poplars have a number of good characteristics, including fast growth rate, high yield, many use...Poplars are among the most important deciduous tree species in China. China is replete with natural resources of poplars. Poplars have a number of good characteristics, including fast growth rate, high yield, many uses, easiness of tissue culture and small gene group that make them well suited as a model system for the application of genetic engineering in forest trees. In the last decade, much progress has been made in genetic improvement of poplar species in China. Modern biotechnology is an important tool for genetic improvement in forest trees, and its applications to genetic improvement in poplars, which covers genetic transformation, gene expression, construction of genetic linkage map, QTLs (quantitative trait loci) identification and molecular assisted selection are reviewed in this paper. At the same time, the existing problems and outlook about the application of modern biotechnology to genetic improvement in forest trees are also discussed.展开更多
AIM: To estimate the frequency of microdeletions in the long arm of Y-chromosome of 20 infertile males from South India. METHODS: Polymerase chain reaction (PCR) amplification using Y-specific STS of azoospermia facto...AIM: To estimate the frequency of microdeletions in the long arm of Y-chromosome of 20 infertile males from South India. METHODS: Polymerase chain reaction (PCR) amplification using Y-specific STS of azoospermia factor (AZF) regions i.e., SY 84 for AZFa, SY 127 for AZFb and SY 254 for AZFc. RESULTS: Of the 20 infertile subjects 3 (15 %), one azoospermic and two oligozoospermic, showed microdeletions in the AZF region of Y-chromosome. CONCLUSION: The frequency of deletions involving AZF region of the Y-chromosome is 15 % in azoospermic and severely oligozoospermic infertile men. PCR amplification of AZF locus is useful for the diagnosis of microdeletions in the Y-chromosome.展开更多
<strong>Introduction:</strong> The goal of this study was to utilize physical characteristics instead of placing subjects in arbitrary diagnostic categories to test for associations with genetic variants. ...<strong>Introduction:</strong> The goal of this study was to utilize physical characteristics instead of placing subjects in arbitrary diagnostic categories to test for associations with genetic variants. <strong>Methods:</strong> Forty-four single nucleotide polymorphisms were tested for association with specific cephalometric measurements in thirty-nine University of Pittsburgh Dental Registry and DNA Repository orthodontic subjects. Cephalometric measurements included an evaluation of FMA, a Wits appraisal, and a Steiner’s ANB analysis. Genetic markers were genotyped using polymerase chain reaction and Taqman chemistry. Chi-square and Fischer’s exact tests (α = 0.05) were used in investigation of overrepresentation of marker alleles. Samples were divided into groups based upon having an FMA, Wits, or ANB measurement above or below the mean of the cohort studied. Secondary analysis was done for sex and ethnicity to determine their effect on FMA, Wits, or ANB. <strong>Results: </strong>An association between FMA measurements was discovered in the following genes: ACTN3, CASP4, ESR1, FGF13, KRT7, and PITX2. An association between Wits measurements was discovered in the following genes: ACTN2, BTBD11, CASP4, FGF3, and FGF10. No associations were found with ANB.<strong> Conclusions: </strong>Genetic markers in several genes at different loci may contribute to craniofacial deformities in humans. This approach of using physical measurements may be an advantage to placing patients in arbitrary diagnostic categories.展开更多
A population of 152 recombinant inbred lines (RIIs) derived from a cross between CT9993, a japonica rice with hard consistency (GC) and Khoa Dawk Mali105 (KDML 105 ), a famous Thai rice(Oryza sativa L. ) with medium G...A population of 152 recombinant inbred lines (RIIs) derived from a cross between CT9993, a japonica rice with hard consistency (GC) and Khoa Dawk Mali105 (KDML 105 ), a famous Thai rice(Oryza sativa L. ) with medium GC, was used for GC quantitative trait loci (QTLs) analysis. Three linkage maps were constructed with RFLP, AFLP and microsatellite (SSLP) markers. The first one consists of 83 RFLP markers with 17.53 cM of an average distance between markers. The second one consists of 83 RFLP and 69 AFLP markers with 13.22 cM average distance between markers and the third one consists of 83 RFLP, 69 AFLP and 15 SSLP markers, and has an average distance of 12.98 cM between markers. Based on these three maps, QTLs conferring GC were analyzed. The results show that GC is mainly controlled by two linked loci,which are located at the two flanks of RFLP marker R2170 on chromosome 3. The distance between the two linked QTLs is 25 cM and the two QTLs were determined by a LOD scores larger than 16.0. The number of minor QTIs controlling GC varies from 4- 9 in the three different linkage maps.展开更多
The yellow color of the cocoon of the silkworm Bombyx mori is controlled by three genes, Y （Yellow haemolymph）, 1 （Yellow inhibitor） and C （ Outer-layer yellow cocoon）, which are located on linkage groups 2, 9 a...The yellow color of the cocoon of the silkworm Bombyx mori is controlled by three genes, Y （Yellow haemolymph）, 1 （Yellow inhibitor） and C （ Outer-layer yellow cocoon）, which are located on linkage groups 2, 9 and 12, respectively. Taking advantage of a lack of crossing over in females, reciprocal backcrossed F1 （BC1） progeny were used for linkage analysis and mapping of the C gene using silkworm strains C 108 and KY, which spin white and yellow cocoons, respectively. DNA was extracted from individual pupae and analyzed for simple sequence repeat （SSR） markers. The C gene was found to be linked to seven SSR markers. All the yellow cocoon individuals from a female heterozygous backcross （BC1F） showed a heterozygous profile for SSR markers on linkage group 12, whereas individuals with light yellow cocoons showed the homozygous profile of the strain C108. Using a reciprocal heterozygous male backcross （BC1M）, we constructed a linkage map of 36.4 cM with the C gene located at the distal end, and the closest SSR marker at a distance of 13.9 cM.展开更多
Objectives To formulate an equation for fine mapping of disease loci under complex conditions and determine the marker-disease distance in a specific case using this equation. Methods Lewontin’s linkage disequi...Objectives To formulate an equation for fine mapping of disease loci under complex conditions and determine the marker-disease distance in a specific case using this equation. Methods Lewontin’s linkage disequilibrium (LD) measure D’ was used to formulate an equation for mapping disease genes in the presence of phenocopies, locus heterogeneity, gene-gene and gene-environment interactions, incomplete penetrance, uncertain liability and threshold, incomplete initial LD, natural selection, recurrent mutation, high disease allele frequency and unknown mode of inheritance. This equation was then used to determine the distance between a marker (ε4 within the apolipoprotein E gene, APOE) and Alzheimer’s disease (AD) loci using published data.Results An equation was formulated for mapping disease genes under the above conditions. If these conditions are present but ignored, then recombination fraction θ between marker and disease loci will be either overestimated or estimated with little bias. Therefore, an upper limit of θ can be obtained. AD has been found to be associated with the marker allele ε4 in Africans, Asians, and Caucasians. This suggests that the AD-ε4 allelic LD predates the divergence of peoples occurring 100?000 years ago. With the age of AD-ε4 allelic LD so estimated, the maximal distance was calculated to be 23.2 kb (mean 5.8 kb). Conclusions (1) A method is developed for LD mapping of susceptibility genes. (2) A mutation within the APOE gene itself, among others, is responsible for the susceptibility to AD, which is supported by recent evidence from studies using transgenic mice.展开更多
文摘In this study, we reported the repaid construction of a molecular marker linkage map of rice (Oryza sativa L.). An F-2 population from the cross between Annong S-1 and Nanjing 11 was used to construct a genetic linkage map of rice. Total of 142 newly screened AFLP markers and 30 anchor markers (25 SSR markers and 5 RFLP markers) were mapped on the 12 chromosomes covering 1537.4 cM of rice genome. The average interval between these markers was 9.0 cM. The total work which usually was finished in more than one year was finished within only 3 months by one person. This is the first plant AFLP map developed in China. A new thermosensitive genic male sterile gene in rice, tms5, was Egged and mapped onto chromosome 2 during the development of the linkage map.
基金the National Key Basic Research Project ("973") and the National Natural Science Foundation of China (Grant No. 39725018).
文摘Modeling linkage disequilibria (LD) between genes usually observed in admixed natural populations has been shown an effective approach in high-resolution mapping of disease genes in humans. A prerequisite to obtain accurate estimation of recombination fraction between genesat a marker locus and the disease locus using the approach is a reliable prediction of the proportion of the admixture populations. The present study suggested the use of gene frequencies to predict the estimate of the admixture proportion based on the observation that the gene frequencies are much more stable quantities than the haplotype frequencies over evolution of the population. In this paper, we advanced the theory and methods by which the decay rate of nonlinear term of LD in admixed population may be used to estimate the recombination fraction between the genes. Theoretical analysis and simulation study indicate that, the larger the difference of gene frequencies between parental populations and the more closely the
基金funded by the Project of Hebei Province Science and Technology Support Program,China(17927670H and 16227516D-1)。
文摘Insufficient available phosphorus in soil has become an important limiting factor for the improvement of yield and quality in soybean. The mining of QTLs and candidate genes controlling soybean phosphorus utilization related traits is a necessary strategy to solve this problem. In this study, 11 phosphorus utilization related traits of a natural population of 281 typical soybean germplasms and a recombinant inbred line(RIL) population of 270 lines were evaluated under different phosphorus conditions at two critical stages: the four-leaf stage as the seedling critical stage was designated as the Tstage, and the six-leaf stage as the flowering critical stage was designated as the Tstage. In total, 200 single nucleotide polymorphism(SNP) loci associated with phosphorus utilization related traits were identified in the natural population, including 91 detected at the Tstage, and 109 detected at the Tstage. Among these SNP loci, one SNP cluster(s715611375, ss715611377, ss715611379 and ss715611380) on Gm12 was shown to be significantly associated with plant height under the low phosphorus condition at the Tstage, and the elite haplotype showed significantly greater plant height than the others. Meanwhile, one pleiotropic SNP cluster(ss715606501, ss715606506 and ss715606543) on Gm10 was found to be significantly associated with the ratio of root/shoot, root and total dry weights under the low phosphorus condition at the Tstage, and the elite haplotype also presented significantly higher values for related characteristics under the phosphorus starvation condition. Furthermore, four co-associated SNP loci(ss715597964, ss715607012, ss715622173 and ss715602331) were identified under the low phosphorus condition at both the Tand Tstages, and 12 QTLs were found to be consistent with these genetic loci in the RIL population. More importantly, 14 candidate genes, including MYB transcription factor, purple acid phosphatase, sugar transporter and HSP20-like chaperones superfamily genes, etc., showed differential expression levels after low phosphorus treatment, and three of them were further verified by q RT-PCR. Thus, these genetic loci and candidate genes could be applied in markerassisted selection or map-based gene cloning for the genetic improvement of soybean phosphorus utilization.
文摘Resistance to whitebacked planthopper(WBPH)in Chinese japonica riceChunjiang 06(CJ-06)was mediated by sucking inhibitory and ovicidal mecha-nism.The ovicidal reponse was a common self-defense mechanism againstWBPH in japonica.The ovicidal gene and its chromosomal position had alreadybeen identified.The sucking inhibitory nature of CJ-06 caused a definenon-preference behavior of WBPH in fields.A single dominant gene governed
基金This work was supported by Science and Technology Committee of Yunnan Provincethe National Natural Science Foundation of China(Grant No.30021004).
文摘Congenital microphthalmia is a developmental ocular disorder and might be caused by the mutations in the genes involved in eye development. To uncover the genetic cause in a six-generation Chinese pedigree with autosomal dominant congenital microphthalmia, we performed genescan and linkage analysis in this family. Fourteen microsatellite markers on chromosomes 3, 11, 14 and 15 were selected as genetic markers according to the five pre-viously reported loci associated with microphthalmia (MITF, SOX2, PAX6, MCOP and NNO2). The genomic DNA of each member in the pedigree was amplified with 14 pairs of fluorescence labeled primers. Genome screening and genotyping were conducted on ABI377 DNA sequencer and linkage analysis was performed with Linkage software package. All two-point LOD scores of linkage analysis between the suggested disease genes and microsatellite markers were <-2, which indicated that none of the five genes were responsible for microphthalmia in this Chinese family. Microphthalmia in this family may be caused by mutation in a new gene which is essential in eye development.
基金supported by the National Natural Science Foundation of China (Nos. 30871565, 31571737)the China Agriculture Research System (No. CARS-09)the Agricultural Science and Technology Innovation Program (ASTIP) of CAAS
文摘Bruchid beetle(Callosobruchus chinensis) poses a serious threat to the production and storage of mung bean(Vigna radiata). Mapping bruchid resistance(Br) will provide an important basis for cloning the responsible gene(s) and elucidating its functional mechanism, and will also facilitate marker-assisted selection in mung bean breeding. Here, we report the construction of the genetic linkage groups of mung bean and mapping of the Br1 locus using an RIL population derived from a cross between Berken, a bruchid-susceptible line, and ACC41, a bruchid-resistant line. A total of 560 markers were mapped onto 11 linkage groups,with 38.0% of the markers showing distorted segregation. The lengths of the linkage groups ranged from 45.2 to 117.0 c M with a total coverage of 732.9 c M and an average interval of1.3 c M between loci. Br1 was located on LG9 between BM202(0.7 c M) and Vr2-627(1.7 c M).Based on 270 shared SSR markers, most of the linkage groups were assigned to specific chromosomes. These results should further accelerate the genetic study of this crop.
文摘Poplars are among the most important deciduous tree species in China. China is replete with natural resources of poplars. Poplars have a number of good characteristics, including fast growth rate, high yield, many uses, easiness of tissue culture and small gene group that make them well suited as a model system for the application of genetic engineering in forest trees. In the last decade, much progress has been made in genetic improvement of poplar species in China. Modern biotechnology is an important tool for genetic improvement in forest trees, and its applications to genetic improvement in poplars, which covers genetic transformation, gene expression, construction of genetic linkage map, QTLs (quantitative trait loci) identification and molecular assisted selection are reviewed in this paper. At the same time, the existing problems and outlook about the application of modern biotechnology to genetic improvement in forest trees are also discussed.
文摘AIM: To estimate the frequency of microdeletions in the long arm of Y-chromosome of 20 infertile males from South India. METHODS: Polymerase chain reaction (PCR) amplification using Y-specific STS of azoospermia factor (AZF) regions i.e., SY 84 for AZFa, SY 127 for AZFb and SY 254 for AZFc. RESULTS: Of the 20 infertile subjects 3 (15 %), one azoospermic and two oligozoospermic, showed microdeletions in the AZF region of Y-chromosome. CONCLUSION: The frequency of deletions involving AZF region of the Y-chromosome is 15 % in azoospermic and severely oligozoospermic infertile men. PCR amplification of AZF locus is useful for the diagnosis of microdeletions in the Y-chromosome.
文摘<strong>Introduction:</strong> The goal of this study was to utilize physical characteristics instead of placing subjects in arbitrary diagnostic categories to test for associations with genetic variants. <strong>Methods:</strong> Forty-four single nucleotide polymorphisms were tested for association with specific cephalometric measurements in thirty-nine University of Pittsburgh Dental Registry and DNA Repository orthodontic subjects. Cephalometric measurements included an evaluation of FMA, a Wits appraisal, and a Steiner’s ANB analysis. Genetic markers were genotyped using polymerase chain reaction and Taqman chemistry. Chi-square and Fischer’s exact tests (α = 0.05) were used in investigation of overrepresentation of marker alleles. Samples were divided into groups based upon having an FMA, Wits, or ANB measurement above or below the mean of the cohort studied. Secondary analysis was done for sex and ethnicity to determine their effect on FMA, Wits, or ANB. <strong>Results: </strong>An association between FMA measurements was discovered in the following genes: ACTN3, CASP4, ESR1, FGF13, KRT7, and PITX2. An association between Wits measurements was discovered in the following genes: ACTN2, BTBD11, CASP4, FGF3, and FGF10. No associations were found with ANB.<strong> Conclusions: </strong>Genetic markers in several genes at different loci may contribute to craniofacial deformities in humans. This approach of using physical measurements may be an advantage to placing patients in arbitrary diagnostic categories.
文摘A population of 152 recombinant inbred lines (RIIs) derived from a cross between CT9993, a japonica rice with hard consistency (GC) and Khoa Dawk Mali105 (KDML 105 ), a famous Thai rice(Oryza sativa L. ) with medium GC, was used for GC quantitative trait loci (QTLs) analysis. Three linkage maps were constructed with RFLP, AFLP and microsatellite (SSLP) markers. The first one consists of 83 RFLP markers with 17.53 cM of an average distance between markers. The second one consists of 83 RFLP and 69 AFLP markers with 13.22 cM average distance between markers and the third one consists of 83 RFLP, 69 AFLP and 15 SSLP markers, and has an average distance of 12.98 cM between markers. Based on these three maps, QTLs conferring GC were analyzed. The results show that GC is mainly controlled by two linked loci,which are located at the two flanks of RFLP marker R2170 on chromosome 3. The distance between the two linked QTLs is 25 cM and the two QTLs were determined by a LOD scores larger than 16.0. The number of minor QTIs controlling GC varies from 4- 9 in the three different linkage maps.
基金Acknowledgments This project was supported by the National Basic Research （973） Program （grant no. 2005CB121000）, Natural Science Foundation of Jiangsu Province （grant no. BK2006508）, Hi-tech Research and Development Program （863） of China （2006AA10A119）.
文摘The yellow color of the cocoon of the silkworm Bombyx mori is controlled by three genes, Y （Yellow haemolymph）, 1 （Yellow inhibitor） and C （ Outer-layer yellow cocoon）, which are located on linkage groups 2, 9 and 12, respectively. Taking advantage of a lack of crossing over in females, reciprocal backcrossed F1 （BC1） progeny were used for linkage analysis and mapping of the C gene using silkworm strains C 108 and KY, which spin white and yellow cocoons, respectively. DNA was extracted from individual pupae and analyzed for simple sequence repeat （SSR） markers. The C gene was found to be linked to seven SSR markers. All the yellow cocoon individuals from a female heterozygous backcross （BC1F） showed a heterozygous profile for SSR markers on linkage group 12, whereas individuals with light yellow cocoons showed the homozygous profile of the strain C108. Using a reciprocal heterozygous male backcross （BC1M）, we constructed a linkage map of 36.4 cM with the C gene located at the distal end, and the closest SSR marker at a distance of 13.9 cM.
文摘Objectives To formulate an equation for fine mapping of disease loci under complex conditions and determine the marker-disease distance in a specific case using this equation. Methods Lewontin’s linkage disequilibrium (LD) measure D’ was used to formulate an equation for mapping disease genes in the presence of phenocopies, locus heterogeneity, gene-gene and gene-environment interactions, incomplete penetrance, uncertain liability and threshold, incomplete initial LD, natural selection, recurrent mutation, high disease allele frequency and unknown mode of inheritance. This equation was then used to determine the distance between a marker (ε4 within the apolipoprotein E gene, APOE) and Alzheimer’s disease (AD) loci using published data.Results An equation was formulated for mapping disease genes under the above conditions. If these conditions are present but ignored, then recombination fraction θ between marker and disease loci will be either overestimated or estimated with little bias. Therefore, an upper limit of θ can be obtained. AD has been found to be associated with the marker allele ε4 in Africans, Asians, and Caucasians. This suggests that the AD-ε4 allelic LD predates the divergence of peoples occurring 100?000 years ago. With the age of AD-ε4 allelic LD so estimated, the maximal distance was calculated to be 23.2 kb (mean 5.8 kb). Conclusions (1) A method is developed for LD mapping of susceptibility genes. (2) A mutation within the APOE gene itself, among others, is responsible for the susceptibility to AD, which is supported by recent evidence from studies using transgenic mice.
