The effect of mutation on pr function 1. Loss of Pr function(the great majority is seen in (Recessive diseases; (2)diseases involving haploinsufficiency, in which 50%of the gene product is insufficient for normal function; and 3)dominant negative mutations, in which the abnormal protein product interferes with the normal protein product
The Effect of Mutation on Pr Function 1. Loss of Pr function (the great majority): is seen in (1)recessive diseases;(2)diseases involving haploinsufficiency, in which 50% of the gene product is insufficient for normal function; and (3)dominant negative mutations, in which the abnormal protein product interferes with the normal protein product
The effect of mutation on pr function 2. Gain of function are sometimes seen in dominant diseases 3. Novel property (infrequent) 4. The expression of a gene at the wrong time (Heterochronic expression), or in the wrong place(Ectopic expression), or both. (uncommon, except in cancer)
The Effect of Mutation on Pr Function 2. Gain of function: are sometimes seen in dominant diseases. 3. Novel property (infrequent) 4. The expression of a gene at the wrong time (Heterochronic expression), or in the wrong place (Ectopic expression), or both. (uncommon, except in cancer)
MUTATION Mutations in Mutations disrupting Mutations affecting coding region RNA stability gene regulation or dosage RNA splicing Protein abnormal Protein structure normal Decreased Hb Hammersmith (if unstable ->decreased amount) amount CAUSE OF DISEASE aE-thalassemias B-thalassemias Monosomies Increased Tumor-suppressor mutations Loss of protein function amount Hb Kempsey Achondroplasia the great majority) Trisomies Charcot- Marie- Tooth Gain of function disease type 1A HPFH Novel property Many oncogenes (infrequent Inappropriate expression (wrong time, place Ectopic or heterochronic expression (uncommon, except in cancer @ElsevierNussbaumetal:ThompsonandThompsonsGeneticsinMedicine7e-www.studentconsult.com
Hemoglobinopathies Disorders of the human hemoglobins Most common single gene disorders in the world WHO: 5% of the worlds population are carriers for clinically significant hemoglobinopathies Well understood at biochemical and molecular levels
Hemoglobinopathies • Disorders of the human hemoglobins • Most common single gene disorders in the world – WHO: 5% of the world’s population are carriers for clinically significant hemoglobinopatihies • Well understood at biochemical and molecular levels
HbA: a2B2 Globular tetramer MW645KD a-Chain Maps to chromosome 16 Polypeptide length of 141 amino acids 阝 Chain Maps to chromosome 11 Polypeptide length of 146 amino acids
HbA: α2β2 • Globular tetramer • MW 64.5 kD • α-Chain – Maps to chromosome 16 – Polypeptide length of 141 amino acids • β-Chain – Maps to chromosome 11 – Polypeptide length of 146 amino acids