医学遗传学教学课件：Genetic Variation in Individuals.pptVIP

* 利用不同的方法将各种基因确定到染色体的实际位置上。物理图谱：利用反映基因间物理距离的测量方法分布染色体上的基因。低分辨率，就是中期染色体细胞遗传中的带，高分辨率就用DNA的碱基对来计算。 物理图谱内容包括三部分：发生染色体重排的疾病基因的定位和克隆，体细胞杂交进行基因定位；FISH进行基因定位。 * * * 用于连锁分析的遗传marker是怎样的？最初我们研究位于不同染色体不同位点的基因连锁情况，如果二者子阿不同染色体上则在减分1是独立的，会产生50%亲缘性的配子，50%非亲缘性的配子。（Fig8-10） * * * * 是否是Marker2与致病基因连锁。如果是纯合子和多态性单一就不能进行分析。 * * * * * * Lod Scores (Z) L(θ 0.5) Z = log10 L(θ = 0.5) Z ? 3 is considered definitive evidence that two loci are linked( equivalent to greater than 1000:1 odds in favor of linkage) Z ? 1 suggest that the two loci are linked Z ? ?1 suggest that the two loci are unlinked When ?=0，Z at D19S221 is 5.85 which means PAP-A/B locus and D19S221 are tightly linked ( equivalent to greater than 100000:1 odds in favor of linkage) Linkage equilibrium and Disequilibrium Linkage sequilibrium: When the real odds of each allele within the haplotypes is the same as the theoretic. Linkage disequilibrium(LD): Real odds of alleles at different loci presented together on the same haplotype are different from the theoretic. By immigration of a founder who carries the disease allele Disease-containing haplotype 疾病关联单体型 Disease Association study The presence of a particular allele at a locus at increased or decreased frequency in affected individuals compared with controls is known as a disease association. The study method is used to complex disease. Summary(1) Concepts of mutation ,polymorphism and haplotype Categories of Human mutations The origin of mutations Types of gene mutations Mutation Nomenclature Types of Polymorphism in DNA Summary(2) Physical Mapping Methods : Somatic cell hybrids Genetic Mapping Concepts: Linkage, Linkage Analysis, Linkage disequilibrium(LD) Methods : Linkage Analysis Lod Scores (Z) * * * * * * * * * * * Mrna 成熟的过程中需要内含子的剪切，有特定的核苷酸序列，位于GU donor (exon-intron) or AG accepter (intron-exon) 位置 另一种突变是不改变原有的位点，但是在内含子中有碱基突变，产生新的剪切位点。与正确的位点竞争。 * * 突变也可以是由于DNA序列的插入，倒位，融合或者缺失导致。如果涉