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