第二章基因突变（新）.pptVIP

Myotonic dystrophy（强直性肌营养不良） DM1 is caused by an abnormal trinucleotide (CTG) repeat expansion in the DM1 locus on chromosome 19q13.3. DM2 is caused by an abnormal tetranucleotide (CCTG) repeat expansion in the DM2 locus on chromosome 3q21. 强直性肌营养不良由Delege（1890）首先描述。肌强直表现受累的骨骼肌收缩后松弛显著延迟，导致明显的肌肉僵硬，肌电图出现特征性连续高频电位放电现象。 Myotonic dystrophy（强直性肌营养不良的遗传早现） Some triplet repeat diseases normal disease Number of Repeats Disease Sequence 11-34 40-200 Huntington’s disease CAG 7-38 66-1700 Friedreich’s ataxia GAA 6-50 200-1300 Fragile X syndrome CGG 5-35 50-2000 Myotonic dystrophy CTG 10-30 44-81 Spinocerebellar ataxia type 1 CAG （脊髓小脑共济失调） Expansion of CGG repeat in FMR-1 gene causes fragile X syndrome Anticipation（遗传早现）: individual has more repeats than normal (premutation), but not enough to cause disease symptoms. Higher number of repeats causes greater instability, so high risk of having an affected child. Fragile X chromosome（脆性X染色体） Characterizied by satellite regions visible at the ends of metaphase chromosomes. These are due to a long series of CGG triplet repeats. (due to backward slippage of daughter strand) prominent and elongated ears and long face. Most of the affected males have mental retardation, and their testes are larger than normal. Fragile X Syndrome X chromosome has a fragile site that breaks easily Fragile area has over 200 repeats of CGG or CCG in mRNA Mental retardation Long face Protruding ears（招风耳） ◆ 30～40岁发病，也有10多岁或60 岁以后发病； ◆ 有进行性不自主的舞蹈样动作，可合并肌强直； ◆ 可出现神经症状，如抑郁，智能衰退，最终成为痴呆。 Huntington’s chorea （亨廷顿舞蹈病） Allen (46,13) age 50 Linda (6,22) Kristen (64,22) age 40 Ann (64,22) age 39 Andrew (69,6) age 37 Debbie (13,6) Greg (11,19) Nathaniel (72,19) age 35 Bill (8,12) Paula (13,12) Evan (not tested) Christina (93,7) age 26 Joseph (7,6) Jama (7,18) Expansion of the Trinucleotide Repeat for Huntington’s Disease * 12-3-4 12-5-6 * 第二章 基因突变 目的要求 掌握基因突变的概念及基因突变的类型 基因突变的多向性； 复等位基因的形成 基因突变具有可逆性； 基因突变的有害性； 基因突变具有稀有性； 基因的自发突变率为10-