遗传学课件monogenicdiseasea

I II 2 2 3 1.Pedigree 1.1.Pedigree Symbol
Information verified by genetic consultant
Pedigree
Information of family members more than three generations
O4
Influential factor
O5
Estimate of recurrence risk
O6
添加副标题
Emphasis
Dominant (A) & Recessive(a)
Locus & Allele (multiple alleles)
Terminology
Homozygote: AA or aa
Marfan syndrome (MIM 154700) 2. Autosomal Dominant (AD) 2.4. Irregular Dominance
Marfan syndrome (MIM 154700)
Autosomal Dominant (AD) Irregular Dominance
Multiple fracture Osteogenesis imperfecta, typeⅠ(MIM 166200) 2. Autosomal Dominant (AD) 2.4. Irregular Dominance Blue sclera Deafness
Blue sclera
2. Autosomal Dominant (AD) 2.4. Irregular Dominance
2. Autosomal Dominant (AD) 2.4. Irregular Dominance
2. Autosomal Dominant (AD) 2.4. Irregular Dominance
Polydactyly, postaxial, type A1 (MIM 174200)
Autosomal Dominant (AD) Incomplete Dominance
Achondroplasia (MIM 100800) 2. Autosomal Dominant (AD) 2.2. Incomplete Dominance
1 2
I II III
1 2 3
Osteogenesis imperfecta, typeⅠ(MIM 166200)
Multiple fracture
Deafness
1 2 3
1 2 3
1 2
I II III IV
1 2 3
Marfan syndrome (MIM 154700) 2. Autosomal Dominant (AD) 2.4. Irregular Dominance
2. Autosomal Dominant (AD) 2.1. Complete Dominance
Brachydactyly, type A1 (MIM 112500)
（引自高波等，2001）
Brachydactyly, type A1 (MIM 112500) 2. Autosomal Dominant (AD) 2.1. Complete Dominance
Monogenic Disease
Medical Genetics
汇报时间：12月20日
Annual Work Summary Report
Terminology
O1
Pedigree symbol & Pedigree analysis
O2
Pedigree characteristics
O3
Types of AD
1 2 3
1 2 3 4
1 2 3
1 2
I II III IV
Polydactyly, postaxial, type A1 (MIM 174200)
2. Autosomal Dominant (AD) 2.4. Irregular Dominance
Pedigree of AD 2. Autosomal Dominant (AD) 2.1. Complete Dominaneristics
Each affected individual has one affected parent 50% of sibs and offspring are affected Males and females are affected with equal probability Passed in a vertical fashion
2. Autosomal Dominant (AD) 2.1. Complete Dominance
The phenotype of the heterozygote (Aa) will be intermediate between the phenotypes of the two homozygotes (AA or aa).
MN blood group (MIM 111300)
ABO blood group (MIM 110300)
2. Autosomal Dominant (AD) 2.3. Codominance
ABO blood group (MIM 110300)
Genotype
Phenotype(blood group)
1
Achondroplasia (MIM 100800)
2. Autosomal Dominant (AD) 2.2. Incomplete Dominance
Both alleles will be completely expressed in the heterozygote, and the individual has a different phenotype than that of either homozygote.
Autosomal Dominant (AD)
1
2
The phenotype of the heterozygote (Aa) will be indistinguishable from the phenotype of the homozygous (AA) dominant.
Autosomal Dominant (AD) Complete Dominance
Complete penetrance Incomplete penetrance
Forme fruste Skipped generation
Penetrance
2. Autosomal Dominant (AD) 2.4. Irregular Dominance
Expressivity
40
42
45
21
32
Exon: (CAG)n n = 9~ 34, average 20 n = 37~100, average 46
Huntingtin (IT 15): 4p16.3
Dynamic mutation
Huntington disease (MIM 143100)
Expressivity is a term used in genetics to refer to variations in a phenotype among individuals carrying a particular genotype.
2. Autosomal Dominant (AD) 2.4. Irregular Dominance
Investigating the death cause, death age, consanguineous marriage, fetal death, abortion, neonatal death
Pedigree Analysis
AD inheritance are those in which a single copy of a mutant gene on autosome is enough for the trait to be expressed or shown.
Marfan syndrome (MIM 154700) 2. Autosomal Dominant (AD) 2.4. Irregular Dominance
Autosomal Dominant (AD)
2.5. Delayed Dominance Not all genetic disorders are congenital, some are expressed at a characteristic age and others at variable ages.
FUT2 (19q13.33)
Sometime the heterozygote (Aa ) will not show the phenotypes of dominant allele, or show different clinical symptoms of it.
01
Autosomal Dominant (AD) Irregular Dominance
02
Penetrance
Penetrance in genetics is the proportion of individuals carrying a particular variation of a gene (allele or genotype) that also express an associated trait (phenotype).
2. Autosomal Dominant (AD) 2.5. Delayed Dominance
Huntington disease (MIM 143100)
2. Autosomal Dominant (AD) 2.5. Delayed Dominance
(CAG)n
100
38
40
26
27
11
Heterozygote: Aa
Genotype & Phenotype
1.Pedigree
The pedigree is a visual tool for documenting biological relationships in families and the presence of traits or diseases.
14
2
AR inheritance are characterized only in individuals homozygous for the mutant gene on autosome.
01
Autosomal Recessive (AR)
02
Carrier (Aa )
2. Autosomal Dominant (AD) 2.5. Delayed Dominance
Huntington disease (MIM 143100)
1 2 3 4 5
I II III
1 2
1 2 3
1. Pedigree
Proband is the first affected family member who seeks medical attention for a genetic disorder.
Proband (index case)
1. Pedigree 1.1. Pedigree Symbol
AA, AO
A
BB, BO
B
AB
AB
OO
O
2. Autosomal Dominant (AD) 2.3. Codominance
ABO blood group (MIM 110300)
2. Autosomal Dominant (AD) 2.3. Codominance
FUT1 (19q13.33) ABO (9q34)