One or more organ system affected.
Person affected if liability above a threshold.
• Single gene (1% liveborn)
Male
Mutations in single genes (often causing loss of function)
单基因遗传病
Single gene disorders Monogenic disorders
单基因遗传病高级遗传
Classification of Genetic Disorders
Epigenetic modifications？ Other reasons?
Etiology of diseases. For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle.
2. Genes are units of heredity, based in DNA
3. Phenotype (physical or functional abnormalities)
Genotype (DNA change)
4. Autosomal vs X-linked
determined by whether the responsible gene is
➢ Thousands of genes may be involved.
➢ Multiple organ systems affected at multiple stages in gestation.
➢ Usually de novo (trisomies, deletions, duplications) but can be inherited (translocations).
Байду номын сангаас
Dominant/recessive pedigree patterns (Mendelian inheritance).
Can affect structural proteins, enzymes, receptors, transcription factors.
• Chromosomal (0.6% liveborn)
carried on one of the autosomal chromosomes
or on the X chromosome
5. Dominant vs Recessive , based on phenotypic
expression
单基因遗传病高级遗传
Dominant
Heterozygotes with one copy of the altered gene are affected
Classification of genetic disorders
• Multifactorial (common)
Variants in genes causing alteration of function
+ environment
“Environmental” influences act on a genetic predisposition to produce a liability to a disease.
• Mitochondrial
单基因遗传病高级遗传
• Somatic mutations (cancer)
Single gene disorders:
disorders in which inheritance is due to a single mutant gene 1. Mendelian inheritance
Autosomal Recessive
horizontal, multiple sibs affected, usually one generation, consanguinity (+)
risk of affected offspring 25%, carrier 50%
Single gene disorders are caused by defects in one particular gene, and often have simple and predictable inheritance patterns. They affect about 1 per cent of th单e 基po因p遗u传la病ti高on级遗as传a whole.
Recessive
Homozygotes with two copies of the altered gene are affected
X-linked recessive
Males with one copy of the altered gene on the X-chromosome are affected
Male
单基因遗传病高级遗传
Single gene disorders
- High risks to relatives - Dominant/recessive pedigree patterns - Some isolated cases due to new dominant mutations - Structural proteins, enzymes, receptors, transcription factors
Ⅰ 1 2
Ⅱ
1
23
Ⅲ4 1
I:1
I:2
II:1
II:2
II:3
II:5
II:6
II:8
III:1
III:2
IV:1
单基因遗传病高级遗传
单基因遗传病高级遗传
Characteristics of single gene inheritance
Autosomal Dominant
vertical (successive), risk of affected offspring 50% (both sex)