医学遗传学Monogenic disorder.ppt

Short interfering RNA (siRNA) Micro RNA (mirRNA) Double-stranded RNA (dsRNA) Short heterochromatic RNA (shRNA) Transcripts from repeated sequences (Alu, LTR) Ribosomal and transfer RNAs Types of non-protein coding RNAs * XR Duchenne Muscular Dystrophy (DMD)(Also known as Pseudohypertrophic) Definition — One of nine types of muscular dystrophy, a group of genetic, degenerative diseases primarily affecting voluntary muscles. Cause — An absence of dystrophin, a protein that helps keep muscle cells intact. Onset — Early childhood - about 2 to 6 years. Symptoms — Generalized weakness and muscle wasting first affecting the musclesof the hips, pelvic area, thighs and shoulders. Calves are often enlarged. Progression — DMD eventually affects all voluntary muscles, and the heart and breathing muscles. Survival is rare beyond the early 30s. A less severe variant is Becker muscular dystrophy. Inheritance — XR. DMD primarily affects boys (1/3500 world-wide), who inherit the disease through their mothers. Women can be carriers of DMD but usually exhibit no symptoms. DMD DMD: Gower’s maneuver Genetics of DMD occurring in about 1 in 3500 males, onset in early childhood, death by 3rd decade male births; X-linked recessive, lethal in males 1/3 of patients are new mutants; 2/3 have carrier mothers dystrophin, Xp21, Extremely large gene (more than 2000 kb), 79 exons. High mutation rate, probably due to large size of gene, 60% to 65% of the mutations are deletions, and about 6% are duplications , Allelic mutations in the same gene cause a milder disorder, Becker muscular dystrophy. DMD (OMIM 310200): Xp21.2, 79 Exons, 2.4 mb Other Examples of XR Hemophilia A: a classical example anti Hemophilia factor Ⅷ deficiency. Glucose-6-Phosphate dehydrogenase deficiency (G6PD): G6PD is in the hexose monophosphate pathway, the only NADPH-generation process in mature red cells, which lack the citric acid cycle. For this reason G6PD deficiency has adverse physiologic effects. Defi