遗传性疾病的基因诊断遗传性疾病基因诊断的策略课件.ppt

1、 间接诊断的实质是在家系中进行连锁分析，通过分析可确定个体来自双亲的同源染色体中的哪一条为致病染色体，从而判断该个体是否带有致病基因。间接诊断不是寻找 DNA 的遗传缺陷，而是通过分析DNA的遗传标记的多态性估计被检者患病的可能性。11kb/12kb/12kb/11kb/12kbF基因的直接检测22号内含子倒位检测 长距离PCR扩增22号内含子Bcl I RFLP（血友病（血友病A）F基因连锁分析 F基因st14位点多态性检测B/A/B/CB/CC/DC/B/DPCR检测VNTR（st14）位点进行家系连锁分析C/C50:C49:C45:C44:Cjp:11223C50:C49:C45:C44

2、:Cjp:1221221313C50:C49:C45:C44:Cjp:2112121313C50:C49:C45:C44:Cjp:2112121313C50:C49:C45:C44:Cjp:2112112212C50:C49:C45:C44:Cjp:12212C50:C49:C45:C44:Cjp:21313C50:C49:C45:C44:Cjp:1122312212C50:C49:C45:C44:Cjp:21313C50:C49:C45:C44:Cjp:213131234567891011121314151617181920212223125.8 5.8 2.8 3.4 4.5 4.5 0.

3、9 0.9 0.9 N N N 4.8 4.8 4.8 5 5 55.8 5.8 2.8 5.8 4.5 3.4 4.5 4.5 0.9 0.9 0.9 0.9 N N N N 4.8 4.8 4.8 4.8 5 5 5 5 1 2 3 45.8 2.8 4.8 4.8 1.2 0.9 inv N 5 52.84.80.9-52.84.80.9-55.8 4.8 1.2 inv 55.8 4.8 0.9 N 55.8 4.8 1.2 inv 55.8 4.8 0.9 N 5123456789101112MD是否由Dystrophin缺陷所致是。孕妇是否携带者？是。或可能是。胎儿性别？男孩。分子

4、生物学研究不是。寻找引起本病的原因不是。不进行产前基因诊断，但应研究家系中其他有风险者女孩。不进行分子生物学研究明确诊断先证者，确定引起疾病的分子异常明确诊断先证者，确定引起疾病的分子异常了解本病传递至下代的风险率了解本病传递至下代的风险率判断胎儿是否患病判断胎儿是否患病遗传性代谢病诊断：遗传性代谢病诊断：生化酶学或蛋白（脂类）检测生化酶学或蛋白（脂类）检测基因诊断基因诊断Inherited PKU二氢叶酸还原酶（DHPR）缺乏也可以导致PUKPKU is caused by the lack of an enzyme known as phenylalanine hydroxylase.Th

5、is enzyme is responsible for converting the amino acid phenylalanine to a second amino acid,tyrosine.Tyrosine is involved in the production of the pigment melanin in the skin.Individuals with PKU are unable to make melanin and are,therefore,usually blond haired and blue eyed.When phenylalanine is no

6、t converted to tyrosine,it builds up in the body and is converted instead to a compound known as phenylpyruvate.Phenylpyruvate impairs normal brain development,resulting in severe mental retardation in a person with PKU.The worst symptoms of PKU can be prevented if the disorder is diagnosed early in

7、 life.In that case,a person can avoid eating foods that contain phenylalanine and developing the disorder that would follow.GALT：半乳糖：半乳糖-1-磷酸尿苷酰转移酶磷酸尿苷酰转移酶GAKL1:半乳糖激酶GALE:尿苷-二磷酸半乳糖-4-表异构酶基因诊断基因诊断原发性高脂蛋白血症(primary hyperlipoproteinemia)ApoB48ApoA-ApoB48ApoCApoAApoEApoB48ApoAApoEPL CHEApoA CE、DApoA E、D、CApoB100ApoB100ApoCApoEApoB100ApoEApoB100ApoE 小肠小肠新生新生CM成熟成熟CMCMR肝细胞摄取肝细胞摄取游离脂肪酸游离脂肪酸供肝外组织利用供肝外组织利用LPLApoCApoEApoCTG新生新生HDLLCAT成熟成熟HDL肝肝新生新生VLDLApoCApoE成熟成熟VLDLLPLPL CHApoCCHEIDL游离脂肪酸游离脂肪酸供肝外组织利用供肝外组织利用LDL外周组织摄取外周组织摄取基因诊断基因诊断三羧酸循环氧化磷酸化RNA编码序列等线粒体是生物体获得能量的主要装置线粒体是生物体获得能量的主要装置