1. Genetic Counseling for the Future
SCDAA 40th Anniversary Convention 2012
Genetic Counseling for the Future
Kwaku Ohene-Frempong, MD
Children’s Hospital of Philadelphia
Sickle Cell Foundation of Ghana

2. Genetic Counseling for the Future

3. Genetic Counseling for the Future

4. Hemoglobin Molecule Heme + Globin = Hemoglobin (Hb)
Heme is an iron compound; globin is a protein
Globins in hemoglobin
1 pair of -like globins
+ 1 pair of -like globins
Hb tetramer
-like globin: 141 amino acids
-like globin: 146 amino acids

5. Genetics of Hemoglobinopathies
Human Hemoglobin Genes and Products
-globin gene family
b-globin gene family
Chromosome Globin proteins Chromosome 11
Chromosome Globin proteins Chromosome 11
Chromosome Globin proteins Chromosome 11
Hemoglobins: Birth > 1 yr
F: a2 g % < 2%
A2: a2 d < 1% 2-3%
A: a2 b % 96%
“Embryonic”
“Fetal”
“Minor adult”
“Major adult”

6. Molecular pathology of SCD Hemoglobin Genes and Products in SCD-SS
Sickle Cell Disease: Pharmacologic Treatment
Molecular pathology of SCD Hemoglobin Genes and Products in SCD-SS
Gower 1: z2 e2
Gower 2: a2 e2
Portland: x2 g2
F: a2 g2
A2: a2 d2
S: a2 bs2
2-20% 3%
80-95%
Hemoglobins in SS by age > 1 yr

7. A S A A S S C C A A S C S S C
(AA)

8. A S A A S S C C A S A A A S C S C
(AA)

9. Genetic Counseling for the Future
Outline
Definition of Genetic Counseling
Genetic Counseling and the Modern Family
Modern Genetics of Sickle Cell Disease
Common Variants of Sickle Cell Disease
Diagnostic Tests for Hemoglobin Disorders
Inheritance of Sickle Cell Disease

10. Definition of Genetic Counseling
Genetic Counseling for the Future
Definition of Genetic Counseling
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

11. Definition of Genetic Counseling
Genetic Counseling for the Future
Definition of Genetic Counseling
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:
(accessed )

12. Genetic Counseling and the Modern Family
Genetic Counseling for the Future
Genetic Counseling and the Modern Family
Traditional models:
Married couple – pre-pregnancy, with or without affected child;
Single adult seeking counseling for possible risk
Modern models:
Married couple – pre-pregnancy, with or without affected child;
Single adult seeking counseling because possible risk
WHO:
(accessed )

13. Inheritance of Sickle Cell Disease
When both parents have Sickle Cell Trait (AS)….. A S S A A S A A
… they can have a baby with no abnormal hemoglobin.
(AA) A

14. Inheritance of Sickle Cell Disease
When both parents have Sickle Cell Trait (AS)….. A S S A A S A S
…… they can have a baby with sickle cell trait (AS)
(AS) S A

15. Inheritance of Sickle Cell Disease
When both parents have Sickle Cell Trait (AS)….. A S S A A S A S A
…… they can have a baby with sickle cell trait (AS)
(AS) A S

16. Inheritance of Sickle Cell Disease
When both parents have Sickle Cell Trait (AS)….. A S S A A S A S S
…… they can have a baby with sickle cell disease SS
(SS) S

17. Inheritance of Sickle Cell Disease
When both parents have Sickle Cell Trait (AS)….. A S
each and every time they make a baby,
the baby may have ….
(AA) A
(AS) S A
(SS) S

18. bA bS bC bA bS bC b0 b+ bA bS bA bC bA b0 bA bA bS bC b0 b+ (AA) bA bS

19. Inheritance of Sickle Cell Disease
When both parents have no abnormal hemoglobins or
thalassemia, … bA bA bA bA bA
..all babies they make will have normal hemoglobins.
(AA) bA

20. Inheritance of Sickle Cell Disease
When both parents have Sickle Cell Trait (AS)….. bA bS bA bS bS bA bA bA
… they can have a baby with no abnormal hemoglobin.
(AA) bA

21. Inheritance of Sickle Cell Disease
When both parents have Sickle Cell Trait (AS)….. bA bS bA bS bS bA bA bS
…… they can have a baby with sickle cell trait (AS)
(AS) bA bS

22. Inheritance of Sickle Cell Disease
When both parents have Sickle Cell Trait (AS)….. bA bS bA bS bS bA bS bA bA
…… they can have a baby with sickle cell trait (AS)
(AS) bS bA

23. Inheritance of Sickle Cell Disease
When both parents have Sickle Cell Trait (AS)….. bA bS bA bS bS bA bS bA bS
…… they can have a baby with sickle cell disease SS
(SS) bS

24. Inheritance of Sickle Cell Disease
When one parent has Sickle Cell Trait (AS), and the other has hemoglobin C trait (AC)... bA bC bS
(No S)
… each and every time they make a baby,
the baby may have ….
(AA) bA
(AC) bC bA
(AS) bA bS
(SC) bC bS

25. Inheritance of Sickle Cell Disease
When one parent has beta-zero thalassemia trait,
and the other has Sickle Cell Trait (AS) bA b0 bA bS b0 bA bA bA
… they can have a baby with no abnormal hemoglobin.
(AA) bA

26. Inheritance of Sickle Cell Disease
When one parent has beta-zero thalassemia trait,
and the other has Sickle Cell Trait (AS), ….. bA b0 bA bS b0 bA bA bS
… they can have a baby with sickle cell trait (AS).
(AS) bA bS

27. Inheritance of Sickle Cell Disease
When one parent has beta-zero thalassemia trait,
and the other has Sickle Cell Trait (AS) ….. bA b0 bA bS b0 bA b0 bA bA
..they can have a baby with beta-zero thalassemia trait.
(Ab0) b0 bA

28. Inheritance of Sickle Cell Disease
When one parent has beta-zero thalassemia trait,
and the other has Sickle Cell Trait (AS), ….. bA b0 bA bS b0 bA b0 bA bS
they can have a baby with S beta-zero thalassemia.
(Sb0 thal) b0 bS

29. Inheritance of Sickle Cell Disease
When one parent has beta-zero thalassemia trait,
and the other has Sickle Cell Trait (AS), ….. bA bS b0
(No S)
Each and every time they make a baby,
the baby may have ….
(AA) bA
(AS) bS bA
(Ab0 thal) bA b0
(Sb0 thal) bS b0

30. Inheritance of Sickle Cell Disease
When one parent has Sickle Cell Trait (AS),
and the other has hemoglobin C trait (AC), ….. bA bS bC
(No S)
… each and every time they make a baby,
the baby may have ….
(AA) bA
(AS) bS bA
(AC) bA bC
(SC) bS bC