genetic counseling for the future

SCDAA 40th Anniversary Convention 2012

Genetic Counseling for the Future

Kwaku Ohene-Frempong, MDChildren’s Hospital of PhiladelphiaSickle Cell Foundation of Ghana

Genetic Counseling for the Future

Hemoglobin Molecule

Heme + Globin = Hemoglobin (Hb)

Globins in hemoglobin

-like globin: 141 amino acids

-like globin: 146 amino acids

Heme is an iron compound; globin is a protein

1 pair of -like globins + 1 pair of -like globins

Hb tetramer

Genetics of HemoglobinopathiesHuman Hemoglobin Genes and Products

Chromosome 16 Globin proteins Chromosome 11Chromosome 16 Globin proteins Chromosome 11

-globin gene family

-globin gene family

“Embryonic”

“Fetal”

“Minor adult”

“Major adult”

Chromosome 16 Globin proteins Chromosome 11

F: 2 g2 60-90%< 2%

A2: 2 d2 < 1% 2-3%

A: 2 2 10-40% 96%

Hemoglobins: Birth > 1 yr

Molecular pathology of SCDHemoglobin Genes and Products in SCD-SS

Sickle Cell Disease: Pharmacologic Treatment

Gower 1: z2 e2

Gower 2: 2 e2

Portland: x2 g2

------------------F: 2 g2

A2: 2 d2

S: 2 s2

2-20%

3%

80-95%

Hemoglobins in SS by age > 1 yr

(AA)

SA

A AAS

AA

SS

C C

C

S S

C

(AA)

SA

A AAS

AA

SS

C C

C

S S

C

A ASA

OutlineGenetic Counseling for the Future

1. Definition of Genetic Counseling

2. Genetic Counseling and the Modern Family

3. Modern Genetics of Sickle Cell Disease

4. Common Variants of Sickle Cell Disease

5. Diagnostic Tests for Hemoglobin Disorders

6. Inheritance of Sickle Cell Disease

Definition of Genetic CounselingGenetic Counseling for the Future

Genetic counseling is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease.

This process integrates the following: • Interpretation of family and medical histories to

assess the chance of disease occurrence or recurrence.

• Education about inheritance, testing, management, prevention, resources and research.

• Counseling to promote informed choices and adaptation to the risk or condition

National Society of Genetic Counselors, 2006

Definition of Genetic CounselingGenetic Counseling for the Future

Genetic counseling is the process through which knowledge about the genetic aspects of illnesses is shared by trained professionals with those who are at an increased risk for either having a heritable disorder or of passing it on to their unborn offspring.

A genetic counselor • provides information on the inheritance of illnesses and

their recurrence risks; • addresses the concerns of patients, their families, and

their health care providers; and • supports patients and their families dealing with these

illnesses

WHO: http://www.who.int/genomics/professionals/counselling/en/ (accessed 9-17-12)

http://www.who.int/genomics/professionals/counselling/en/

Genetic Counseling and the Modern FamilyGenetic Counseling for the Future

1. Traditional models:• Married couple – pre-pregnancy, with or without

affected child; • Single adult seeking counseling for possible risk

WHO: http://www.who.int/genomics/professionals/counselling/en/ (accessed 9-17-12)

2. Modern models:• Married couple – pre-pregnancy, with or without

affected child; • Single adult seeking counseling because possible risk

http://www.who.int/genomics/professionals/counselling/en/

AA

(AA)AA

AS

A S

A

SA

When both parents have Sickle Cell Trait (AS)…..Inheritance of Sickle Cell Disease

… they can have a baby with no abnormal hemoglobin.

AA

(AS)SA

AS

A S

S

SA

Inheritance of Sickle Cell Disease

…… they can have a baby with sickle cell trait (AS)

When both parents have Sickle Cell Trait (AS)…..

AS

(AS)AS

AS

A S

A

SA




AS

(SS)

SS

AS

A S

S

SA


…… they can have a baby with sickle cell disease SS


A S SA

(SS)SS

(AA)AA

(AS)SA

(AS)AS

each and every time they make a baby,the baby may have ….

Inheritance of Sickle Cell DiseaseWhen both parents have Sickle Cell Trait (AS)…..

C

A

(AA)

A

A S

A

AA

S

A

S SC C

C

C

S

A

A

A

0

A

0 +

S C

A 0

0

+

+

A AA

A

A

A A

(AA)A A

A A

When both parents have no abnormal hemoglobins orthalassemia, …


..all babies they make will have normal hemoglobins.

A AA

S

A

A S

(AA)A A

A S



A AS

S

A

A S

(AS)A S

A S



S AA

S

A

A S

(AS)S A

A S



S AS

S

A

A S

(SS)S S

A S


…… they can have a baby with sickle cell disease SS

(SC)CS

(AA)AA

(AC)CA

(AS)AS

A CA S

… each and every time they make a baby,the baby may have ….

When one parent has Sickle Cell Trait (AS), and the other has hemoglobin C trait (AC)...

(No S)


A AA

0

A

A S

(AA)A A

A 0

When one parent has beta-zero thalassemia trait, and the other has Sickle Cell Trait (AS)



A AS

0

A

A S

(AS)A S

A 0

When one parent has beta-zero thalassemia trait, and the other has Sickle Cell Trait (AS), …..


… they can have a baby with sickle cell trait (AS).

0 AA

0

A

A S

(A0)0 A

A 0

When one parent has beta-zero thalassemia trait, and the other has Sickle Cell Trait (AS) …..


..they can have a baby with beta-zero thalassemia trait.

0 AS

0

A

A S

(S0 thal)0 S

A 0



they can have a baby with S beta-zero thalassemia.

(S0 thal)S0

(AA)AA

(AS)SA

(A0 thal)A0

A SA 0

Each and every time they make a baby,the baby may have ….

(No S)



(SC)SC

(AA)AA

(AS)SA

(AC)AC

A SA C

… each and every time they make a baby,the baby may have ….

(No S)

When one parent has Sickle Cell Trait (AS), and the other has hemoglobin C trait (AC), …..


genetic counseling for the future

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