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

Genetic Counseling for the Future

Genetic Counseling for the Future

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

Genetics of Hemoglobinopathies Human Hemoglobin Genes and Products -globin gene family b-globin gene family Chromosome 16 Globin proteins Chromosome 11 Chromosome 16 Globin proteins Chromosome 11 Chromosome 16 Globin proteins Chromosome 11 Hemoglobins: Birth > 1 yr F: a2 g2 60-90% < 2% A2: a2 d2 < 1% 2-3% A: a2 b2 10-40% 96% “Embryonic” “Fetal” “Minor adult” “Major adult”

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

A S A A S S C C A A S C S S C (AA)

A S A A S S C C A S A A A S C S C (AA)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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