Lecture #16 10/10 Dr. Wormington

Transcription

1 Lecture #16 10/10 Dr. Wormington Recombination Freq /2300 =0.17 (17%) How Far Apart Are B & Vg? T.H. Morgan 1 st to Construct a Genetic Map Using Recombination Frequencies 1 Map Unit = Recombination Frequency of 0.01 (1%) = 1 centimorgan (cm) What's Wrong With This Slide? (Compare to Fig in text) 1 st off, y,w, & v are misassigned! Clue - Gene letter should match name Note - At least the flies are mapped in the correct places! 2 nd & Most Importantly for this slide and Fig in the text! The Recombination Frequences are 10X too high For the Indicated Map Distances in cm Reduce all the frequencies by 10X to agree with the Map

2 How To Map the Relative Positions of a Series of Linked Genes: Generate a series of test crosses Between all possible pair-wise combinations of available genetic markers Determine Recombination Frequencies % Recombination X100 = Map Distance in cm e.g., for y & w 0.1% (.001) recombination (NOT 0.010) X 100 = 0.1cM Note: 1 gene must be chosen as the 0.0 map reference point e.g. y All Genes Exhibiting Recombination i.e. mapped to a single chromosome Comprise a Linkage Group e.g., y,w,v,m,r Additional Points Concerning Gene Mapping via Recombination Frequencies In General, Physical Distance Correlates With Map Distance ForDrosophila, 1 cm = 3-5 x 10 5 bp DNA = ~6 10 Genes For Humans, 1 cm = 10 6 bp DNA = ~20 Genes Avg Gene Length = 5 x 10 4 bp DNA However, Recombination Frequences Between Very Widely Spaced Genes Are Actually reduced Owing to Multiple Crossover Events Between Them

3 Recombination Freq /2300 =0.17 B & Vg are 17 cm Apart or Separated By ~ genes SeX Determination in Flies XX Female Fertile XXY Female Fertile XY Male Fertile XO Male Sterile X/Autosome Ratio Determines Sex Remember Diploid Cells Contain 2 sets of Autosomes (A) 2X + 2A = X/A =1.0 = Female 1X + 2A = X/A = 0.5 = Male Y Chromsosome Required for Male Fertility Not Sex-Determination

4 SeX-Linked Inheritance in Flies Dominant red-eye Only Single Allele Present Females red-eyed Heterozygotes Males red-eyed Hemizygotes Females red-eyed Heterozygotes Males white-eyed Hemizygotes Sex Determination in Humans XX Female Fertile XO Female Sterile Turner Syndrome XY Male Fertile XXY Male Sterile Klinefelter Syndrome Y Chromosome Contains Maleness-Determining Gene Sex-determining Region on the Y Chromosome (SRY) X Chromosome Contains an "Anti-Male" Gene (DAX1) Dosage-sensitive sex reversal, adrenal hypoplasia congenita critical region on the X chromosome gene 1 Represses Testis Development Permits Ovarian Development Male Sex Determination Due to Negative Regulation of DAX1 by SRY

5 SeX-Linked Inheritance in Humans 3 of 5 Possible Scenarios Males Normal Females Carriers Males Normal Males Mutant Females Normal Females Carrier Males Mutant Females Carriers How to Generate Mutant Females? SeX-Linked Inheritance in Humans 2 Additional Scenarios Mutant Male X Mutant Female All Progeny Mutant Mutant Male X Carrier Female Males Normal Males Mutant Females Carrier Females Mutant

6 Thank Your Mom Or Your Maternal Grandfather! Examples of Disease-Related Genes on the X Chromosome Amelogenesis imperfecta Alport syndrome Anhidrotic ectodermal dysplasia Chronic granulomatous disease Combined Immune Deficiency Congenital hypertrichosis Diabetes insipidus Duschenne Muscular Dystrophy Fabry Disease G6PD Deficiency Hemophilia A Hemophilia B Hunter Syndrome Hypophosphatemia Icthyosis Incontinentia pigmenti Lesch-Nyhan Syndrome Menkes Disease Ornithine transcarbamylase deficiency Red/Green Colorblindness Retinitis Pigmentosa Rett syndrome Abnormal tooth enamel Deafness, Inflamed kidney tubules Absence of teeth, hair & sweat glands Skin/lung infections; enlarged liver & spleen Lack of Immune cells Dense hair over entire body Excessive urination, electrolyte imbalance Progressive muscle weakness & debilitation Skin lesions, abdominal pain, kidney failure Hemolytic anemia after eating fava beans Lack Clotting Factor VIII Lack Clotting Factor IX Deformed face, dwarfism, deafness, retardation Vitamin D-resistant rickets Rough scaly skin over entire body Swirls of skin color, hair loss, seizures Mental retardation, self-mutilation Abnormal copper transport, brain atrophy Mental deterioration, excessive ammonia levels Abnormal green/red retinal pigments Retinal Degeneration & Progressive Blindness Mental retardation, neurodegeneration DNA = Genetic Material & Mechanism of Replication Series of "Classical" Studies in Molecular Biology Avery, MacLeod & McCarty 1944 Griffith's "Transforming Principle" is DNA Hershey & Chase 1952 "Waring Blendor" Experiment DNA is Genetic Material Chargaff 1950 "Chargaff's Rule" Total Pyrimidines (C+T) = Total Purines (A+G) in DNA Watson & Crick 1953 Deduce Double Helical Structure of DNA from X-ray Crystal Structure Derived by Wilkins & Franklin Meselson & Stahl 1957 DNA Replication is Semi-Conservative

7 Griffith (1920s) 1 st Demonstrates Genetic Transformation Avery et al (1944) Demonstrate DNA is Transforming Principle Electron Micrograph of a T2 Bacteriophage Infecting an E.coli Cell Head w/ DNA Neck/Collar Sheath Base Plate Tail Fiber