genetic counseling for the future
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Genetic Counseling for the FutureTRANSCRIPT
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
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)
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
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
Inheritance of Sickle Cell Disease
…… they can have a baby with sickle cell trait (AS)
When both parents have Sickle Cell Trait (AS)…..
AS
(SS)
SS
AS
A S
S
SA
Inheritance of Sickle Cell Disease
…… they can have a baby with sickle cell disease SS
When both parents have Sickle Cell Trait (AS)…..
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, …
Inheritance of Sickle Cell Disease
..all babies they make will have normal hemoglobins.
A AA
S
A
A S
(AA)A A
A S
When both parents have Sickle Cell Trait (AS)…..Inheritance of Sickle Cell Disease
… they can have a baby with no abnormal hemoglobin.
A AS
S
A
A S
(AS)A S
A S
When both parents have Sickle Cell Trait (AS)…..Inheritance of Sickle Cell Disease
…… they can have a baby with sickle cell trait (AS)
S AA
S
A
A S
(AS)S A
A S
When both parents have Sickle Cell Trait (AS)…..Inheritance of Sickle Cell Disease
…… they can have a baby with sickle cell trait (AS)
S AS
S
A
A S
(SS)S S
A S
When both parents have Sickle Cell Trait (AS)…..Inheritance of Sickle Cell Disease
…… 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)
Inheritance of Sickle Cell Disease
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)
Inheritance of Sickle Cell Disease
… they can have a baby with no abnormal hemoglobin.
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), …..
Inheritance of Sickle Cell Disease
… 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) …..
Inheritance of Sickle Cell Disease
..they can have a baby with beta-zero thalassemia trait.
0 AS
0
A
A S
(S0 thal)0 S
A 0
When one parent has beta-zero thalassemia trait, and the other has Sickle Cell Trait (AS), …..
Inheritance of Sickle Cell Disease
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)
When one parent has beta-zero thalassemia trait, and the other has Sickle Cell Trait (AS), …..
Inheritance of Sickle Cell Disease
(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), …..
Inheritance of Sickle Cell Disease