Class Notes (838,036)
Biology (2,437)
BIOLOGY 2C03 (138)
Lecture

# Molecular Genetics of Sickle Cell Disease.docx

6 Pages
130 Views

School
Department
Biology
Course
BIOLOGY 2C03
Professor
Bhagwati Gupta
Semester
Fall

Description
September 12 , 2013 Biology 2C03: Genetics Molecular Genetics of Sickle Cell Disease Let’s Review What we Learned Last Class with an Example - P generation: perform a cross between two black-furred rabbits. In the F1 generation you get 6 black-furred offspring and two white-furred offspring.  What is the pattern of inheritance?  Recessive  What is the genotypic ratio in the black-furred offspring?  1 B/B:2B/b genotypic ration among the black F1 progeny  What if you wanted to breed white-furred rabbits, but white-furred rabbits have reduced fertility, what would you do next?  Breed heterozygous parents - F1 generation: perform a cross between two black-furred rabbits from the F1 progeny. What is the probability of white-furred offspring in the F2?  To get a white rabbit, both rabbits must be B/b in genotype and a b/b offspring must be produced by these parents  We need to calculate two probabilities: 1) Probability the parents are heterozygous  There will be a 1/3 chance that the F1 black rabbit is B/B and a 2/3 chance that the black rabbit is B/b 2) Probability heterozygous parents will produce b/b offspring  The chance of two B/b parents giving offspring is ¼  P (white offspring) = P(both F1 rabbits are B/b) x P(b/b offspring) – (2/3 x 2/3) x (1/4) = 1/9 Sickle Cell Disease is an Autosomal Recessive Disorder - Clues to look for in a pedigree for autosomal recessive inheritance: 1) Usually appears in both sexes with equal frequency 2) Tends to skip generations 3) Affected offspring usually born unaffected parents 4) When both parents are heterozygous, approximately ¼ children affected (if there is more than ¼, suggest that it may be dominant) - Other patterns of inheritance  Autosomal dominant traits  X-chromosome linked inheritance Molecular Basis of Inheritance of SCD - Sickle cell anemia is a hereditary disorder inherited in an autosomal recessive manner - What is the molecular basis of inheritance? - James Neel (1949) examined the parents of children with SCD - Hypothesized if SCD was produced by an autosomal recessive allele, the parents of SCD are heterozygous carriers Neel’s Hypothesis - Neel predicted that since parents are heterozygotes they may have some sickled cells - After examination, all 42 parents had sickled cells in their blood  Not completely autosomal recessive - This is sometimes referred to as Sickle Cell Trait and these individuals are heterozygous carriers of the sickle cell allele Hereditary Variation can be Studied at the Molecular Level - 1949 Pauling published study in Science entitled “Sickle Cell Anemia, a Molecular Disease” - Showed haemoglobin from patients with SCD has a different electrical charge than haemoglobin from healthy individuals - First time “abnormal” protein was linked to a disease and that genes determined protein structure  Found that DNA within the cell determines protein structure - Fifty years later still discussed in medical and biology textbooks (and genetics lectures Molecular Identification of SCD - Hemoglobin variants were identified - Homozygous: 1 band - Heterozygous: two bands = two hemoglobim variants that have two charges - Homozygous: more negative charge - This is consistent with a small difference in the charge of the protein - The amount of a protein in a band on the gel can be quantified using densitometry - Each peak represents a band on the electrophoretic gel  Two peaks for heterozygous  Mixing mutant and wildtype would result in the two peaks observed in a heterozygous individual - Pauling performed two-dimensional paper chromatography of normal haemoglobin A and sickle cell haemoglobin S - Separated based on size and charge which is how they identified which amino acid was responsible - All the spots were the same except for one spot - Vernon Ingram (father of molecular medicine) analyzed peptide one amino acid at a time: glutamic to a valine - Showed sickle cell haemoglobin differs by a single amino acid, the number 6 position, in the β chain of hemoglobin Molecular Genetics - The importance of Pauling’s work: 1) Identified laboratory methods for the detection of distinct forms of haemo
More Less

Related notes for BIOLOGY 2C03
Me

OR

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Join to view

OR

By registering, I agree to the Terms and Privacy Policies
Just a few more details

So we can recommend you notes for your school.