counseling
TRANSCRIPT
Genetic Counseling
Weiying Jiang Department of Medical Genetics
P253
Genetic counseling should be provided by a medical specialist who has been trained in genetic counseling.
Definition of Genetic counseling
An educational counseling process for
individuals and families who have a genetic
disease or who are at risk for such a
disease.
Genetic counseling: What should we do?
The medical diagnosis and its implications in terms of prognosis and treatment.
The mode of inheritance of the disorder and the risk of developing and transmitting it.
The choice or option available for dealing with the risk.
Genetic counseling: What should we do?
Evaluation of the family history
Discussion of the importance of testing other family members who are at risk for or to be a carrier.
Establishing the diagnosis
Taking a history
Examination
Investigation
laboratory tests
Taking a history
Family history
Personal medical history
Genetic counseling: physical examination
Neonatal screening
Genetic counseling: laboratory tests
Prenatal diagnosis: Cytogenetics, biochemistry, DNA, and/or other testing;
Genetic counseling: Genetic heterogeneity
A similar phenotype being caused by more than one genetic mechanism. Most commonly used for a similar phenotype being caused by mutations in different genes. Allelic heterogeneity refers to different mutations in the same gene.
Genetic counseling: Genetic heterogeneity
Hearing loss Non-special mental retardation
How to do genetic counseling?
A standard prenatal screening test showed the alpha fetoprotein increased.
The mother has had two or more miscarriages or babies that died in infancy
•The mother is 35 when the baby is born.
Chances of having a child with Down syndrome
increase with the mother's age
a woman has a 1 in 350 chance of conceiving a child
with Down syndrome at age 35, a 1 in 110 chance at
age 40, and a 1 in 30 chance at age 45.
How to do genetic counseling?
Down’ syndromeDown’ syndrome
How to do genetic counseling?
•Genetic defects that occur frequently in certain
population.
•Either parent already has children with birth defects or genetic disorders
How to do genetic counseling?
1 . Genotype - Known : estimating the probability of recurrence risk by Mendelian law
AD , AR , XD , XR
2. Genotype - Unknown :estimating the probability of recurrence risk by Bayes law
Genetic counseling: Calculating and presenting the risk (P330)
AD
Known-Genotype
1/2
AR
¼ patient ; ¼ normal ; ½ carrier
Normal phenotype
carrier = (2/4)/(1/4+2/4)=2/3
AR
2/3
1/3 2/3
1/2
1/4
XD
XD
1/2 1/2
XR
Genetic counseling: Calculating and presenting the risk (P330)
Please pay attention to the followings:
Delayed age of onset
Reduced penetrance
Expressivity
Phenocopy
Pleiotropy
Table 22.2 Bayesian calculation for in Fig.22.2Ⅱ⒈
Probability Ⅱ⒈is heterozygous Ⅱ⒈ is not heterozygous
Prior 1/2 1/2
Conditional
Not affected 1-P 1
Joint 1/2(1-P) 1/2
posterior 1/2(1-P) 1/2(1-P)+1/2∻=(1-p) (2-p)∻
Genetic counseling: Calculating and presenting the risk (Reduced penetrance) (p332)
Table 22.3 Bayesian calculation for in Ⅱ⒈Fig.22.4
Probability Ⅱ⒈is heterozygous
Ⅱ⒈ is not heterozygous
Prior 1/2 1/2
Conditional
Unaffected at age 50 years
1/2 1
Joint 1/4 1/2
posterior 1/4 (1/4+1/2∻)=1/3
Genetic counseling: Calculating and presenting the risk (Delayed age of onset) (p332)
DMD- Heterozygote
0
10
20
30
40
50
60
70
80
1 2 3 4
NornalHterozygote
CK: µMol/L
Num
bers
of
the
hete
rozy
gote
Table 22.5 Bayesian calculation for in Fig.22.1Ⅱ⒉
Probability Ⅱ⒉ is a carrier Ⅱ⒉ is not a carrier
Prior 1/2 1/2
Conditional
Three healthy sons
1/8 1
Normal creatine kinase
1/3 1
Joint 1/48 1/2
posterior 1/48 (1/48+1/2)∻=1/25
Genetic counseling: Calculating and presenting the risk (X-linkage recessive inheritance) p336
Phenocopy:
1.An environmental condition that imitates
(copies) one produced by a gene.
2. The person who has an environmentally-
produced condition that mimics one produced
by a gene.
Genetic counseling: Calculating and presenting the risk (P330)
Noise
Definition of pleiotropy:
The phenomenon
whereby a single
mutation affects several
apparently unrelated
aspects of the phenotype .
Genetic counseling: Calculating and presenting the risk (P330)
Genetic counseling: Quantification (p255)
1 in 4
An odds ratio of 3 to 1 against
Genetic counseling: Quantification (p255)
Tail
(50% chance)
Head
(50% chance)
Genetic counseling: Qualification (p255)
Normal Abnormal
Genetic counseling: Discussing the option
Establishing the diagnosis
Discussing the risk of occurrence and reoccurrence
Counselor provide all information
Genetic counseling: Discussing the option
Making informed decision by consultants
Genetic counseling: Special problems
Consanguinity:
1/2
1/4
1/8
1/2
1/4
1/8
1/64 Total probability= 1/64+ 1/64=32
Genetic counseling: Special problems
Incest
Brother –Sister parent– child
Marriage between first degree relatives is forbidden
Genetic counseling: Special problems
Adoption
Genetic counseling: Special problems
Disputed paternity