TAILIEUCHUNG - Chapter 062. Principles of Human Genetics (Part 24)

Nucleotide Repeat Expansion Disorders Several diseases are associated with an increase in the number of nucleotide repeats above a certain threshold (Table 62-6). The repeats are sometimes located within the coding region of the genes, as in Huntington disease or the X-linked form of spinal and bulbar muscular atrophy (SBMA, Kennedy syndrome). In other instances, the repeats probably alter gene regulatory sequences. If an expansion is present, the DNA fragment is unstable and tends to expand further during cell division. The length of the nucleotide repeat often correlates with the severity of the disease. When repeat length increases from one. | Chapter 062. Principles of Human Genetics Part 24 Nucleotide Repeat Expansion Disorders Several diseases are associated with an increase in the number of nucleotide repeats above a certain threshold Table 62-6 . The repeats are sometimes located within the coding region of the genes as in Huntington disease or the X-linked form of spinal and bulbar muscular atrophy SBMA Kennedy syndrome . In other instances the repeats probably alter gene regulatory sequences. If an expansion is present the DNA fragment is unstable and tends to expand further during cell division. The length of the nucleotide repeat often correlates with the severity of the disease. When repeat length increases from one generation to the next disease manifestations may worsen or be observed at an earlier age this phenomenon is referred to as anticipation. In Huntington disease for example there is a correlation between age of onset and length of the triplet codon expansion Chap. 360 . Anticipation has also been documented in other diseases caused by dynamic mutations in trinucleotide repeats Table 62-6 . The repeat number may also vary in a tissue-specific manner. In myotonic dystrophy the CTG repeat may be tenfold greater in muscle tissue than in lymphocytes Chap. 382 . Table 62-6 Selected Trinucleotide Repeat Disorders Disease us Loc peat Re Triple t Length Normal Dis ease ance Inherit Gene Product X-chromosomal spinobulbar muscular atrophy SBMA 1-q12 Xq1 G CA 11- 34 40-62 XR Andro gen receptor Fragile X-syndrome Xq2 G CG 6- 50 200-300 XR FMR- 1 protein FRAXA Fragile X-syndrome FRAXE Xq2 8 GC C 6- 25 200 XR FMR- 2 protein Dystrophi a myotonica DM 19q1 CT G 5- 30 200-1000 AD variable penetrance Myot onin protein kinase Huntingt on disease HD 4p16 .3 CA G 6- 34 37-180 AD Hunti ngtin Spinocere bellar ataxia type 1 SCA1 6p21 . CA G 6- 39 40-88 AD Ataxi n 1 Spinocere bellar ataxia type 2 SCA2 12q2 CA G 15- 31 34-400 AD Ataxi n

• Y học thường thức
• Principles of Human Genetics
• bệnh học và điều trị
• bài giảng bệnh học
• tài liệu y khoa
• Harrisons Internal Medicine
• Biological information
• Lecture Genetics
• Human genetics
• Modern genetic techniques
• Mendels principles
• Mendels principles of heredity