Lecture #16 – 10/10 – Dr. Wormington
Recombination Freq.
206+185/2300
=0.17 (17%)
How Far Apart Are B & Vg?
T.H. Morgan 1st 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.10.23 in text)
1st off, y,w, & v are misassigned! Clue - Gene letter should match name
Note - At least the flies are mapped in the correct places!
2nd & Most Importantly for this slide and Fig.10.23 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
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
• For Drosophila, 1 cM = 3-5 x 105 bp DNA = ~6 – 10 Genes
•For Humans, 1 cM = 106 bp DNA = ~20 Genes
•Avg Gene Length = 5 x 104 bp DNA
• However, Recombination Frequences Between Very Widely Spaced Genes
Are Actually reduced Owing to Multiple Crossover Events Between Them
Recombination Freq.
206+185/2300 =0.17
B & Vg are 17 cM
Apart or Separated
By ~100–170 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
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
SeX-Linked Inheritance in Humans
3 of 5 Possible Scenarios
Males Normal
Females Carriers
50:50 Probability
Males Normal
Males Mutant
50:50 Probability
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
50:50 Probability
Males Normal
Males Mutant
50:50 Probability
Females Carrier
Females Mutant
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
Griffith (1920s) 1st 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