Biology 1115 Lecture Notes

Chapter 15: Chromosomal Basis of Inheritance

Outline

• Discovery of sex-linked genes
• Linked genes tend to be inherited together because they are located on the same chromosome
  
• Geneticists use recombination data to map a chromosome's genetic loci.
  
• Using crossover data to construct genetic maps
  
• Chromosomal basis of sex produces unique patterns of inheritance
  
• Sex-linked disorders in humans
  
• Alterations of chromosome number
• Alteration of chromosome structure
  

Mendel's work remained undiscovered until 1900's, when others independently stumbled on similar results. During 1875-1890's, work on cytogenetics led to discovery of chromosomes and their behavior during mitosis and meiosis. Led to a convergence in cytology and genetics. Several parallels noted between Mendel's 1st and 2nd law and chromosome behavior (Fig 15.2):

• 1. chromosomes and genes are both present in pairs in diploid cells
  
• 2. homologous chromosomes separate and alleles segregate during meiosis.
  
• 3. fertilization restores paired condition for both chromosomes and genes.

Chromosome theory of inheritance = mendelian genes have specific loci on chromosomes; it is chromosomes that undergo segregation and independent assortment.

Thomas Hunt Morgan (Early 20th century): used genetic crosses involving the fruitfly Drosophila melanogaster to prove mendel's genes reside on chromosomes.

Drosophila melanogaster

• convenient study organism because:
  
  • prolific breeders
    
  • small size
    
  • 2-week generation time
    
  • small # chromosomes (n=4)
    
  • sex determined by XY system (as in mammals)
    
• Morgan isolated single male fly with white eyes (normally red).
  
• Genetic symbols:
  
  • gene takes the symbol from first mutant
    
  • "+" denotes most common allele (wildtype)
    
  • upper and lower case denote dominant/recessive of mutant.

Discovery of sex-linked genes

• Morgan crossed made the following cross:

white eye male x red eye female;all F1 with red eyes;F2 show 3:1 ratio of red to white, BUT only males had white eyes, i.e eye color correlated with sex EXPLANATION of F2 results: eye color present of X chromosome. Genes located on a sex-chromosome are called sex-linked genes

Morgan also performed a reciprocal cross ( phenotypes of parental generation were reverersed). He made predictions of the outcome assuming the eye-color gene was located on the X-chromosome. His results matched his predictions.

Linked genes tend to be inherited together because they are located on the same chromosome

• Number of genes is much greater than the number of chromosomes. Each chromosomes has 1000's of genes.
  
• when geneticists follow linked genes in breeding experiments, results deviate from those expected according to the mendelian principle of independent assortment.
  
• To show that linked genes are inherited together, Morgan did following cross (Fig 15.5)

This is a testcross :if unlinked Expect 1:1:1:1 of b+b vg+vg b b vg vg b+b vg+vg b b vg vg ACTUAL results were: 965 b+b vg+vg 944 b b vg vg 206 b+b vg+vg 195 b b vg vg

• Recombinants result from chromosome crossing over during prophase I of meiosis.
  
• Based on such results, concluded that these two genes are ordinarily on the same chromosome, but recombination unlinks them.
  
• When 1/2 of progeny are recombinant, we say that there is a 50% recombination frequency, and the genes in a cross behave as if on different chromosomes altogether.

Geneticists can use recombination data to map a chromosome's genetic loci.

• Genetic map = lists a sequence of genetic loci along a particular chromosome.
• Alfred Surtevant: Morgan's student reasoned that different recombination frequencies reflect different distances between genes on a chromosome ( Fig 15.6).
  • the farther apart genes are, the greater likelyhood of X-over
    
  • the closer together two genes are, the less likely of X-over occurring.
• Map unit = 1% recombination frequency (centimorgan)
• recombination frequency =( # recombinants) (100%) /total offspring
  

Using crossover data to construct genetic map

• Refer to Fig 15.7
• Suppose you know the distance between two genes:
  
• Suppose also that another gene (cn) is known to be close to b. The question is how do you know to which side cn is of b with respect to the vg gene.
• (Fig 15.8)
  
• linkage map = genetic map based on recombination frequencies
• cytological map = actually pinpoints genes along on chromosomes

NOTE: because X-over frequency is not constant along all areas of the chromosome, 1 map unit does not actually correspond to a fixed length of chromosome.

Chromosomal basis of sex produces unique patterns of inheritance

In mammals, there are two types of sex chromosomes: XX are female, XY are male (Fig 15.9).

Sex-linked disorders in humans

• Not all genes on X chromosome are involved in sex determination (Fig 15.9).
  
• Genes on sex chromosomes are said to be sex-linked (X-linked or Y-linked)
• Examples of Recessive X-linked disorders:
  
  • 1. Hemophilia
    
    • defined by lack of a protein involved in blood clotting.
      
    • plagued much of royal families of europe
      
  • 2. Duchene muscular distrophy
    
    • 1/3500 males in US
      
    • more common in males than females
      
    • characterized by progressive weakening of muscles and loss of coordination.
      
    • lack a muscle protein known as dystrophin

Inactivation of X chromosome in females

• To compensate for dosage differences between male and female for X-linked genes, in females one of the X chromosomes is randomly inactivated early in development. The inactivated chromosome can be seen at the periphery of the nucleus and is called a Barr body. Females are a mosaic for X chromosome.

Alterations of chromosome number

• Alterations in chromosome number result from nondisjunction (pairs of chromosomes fail to separate at meiosis)(Fig 15.12).
  
• Aneuploidy = having + or - normal number chromosomes (monosomics vs trisomics).
  
• Chromosome deletions are usually lethal
  
• Other chromosome aberrations may as lethal; some survive (e.g trisomy 21)
  
• Polyploidy = when organism has more than 2 complete sets of chromosomes. Originate by genome doubling. (haploid, diploid, triploid, tetraploid)
• Human disorders due to chromosomal alterations
  
  • Down syndrome; 1/700 children affected; extra chromosome 21; retardation to various drgrees; correlated with age of mother.
    
  • Trisomy 13; 1/500; rarely survive more than a year.
    
  • XXY males (Klinefelters syndrome): 1/2000; have male sex organs, but are abnormally small; breast enlargement and other female characteristics; normal intelligence.
    
  • XYY males; taller than average
    
  • XXX females; 1/1000; indistinguishable from XX
    
  • X females (Turner's syndrome): 1/1000; phenotypically female but sex organs do not mature and are sterile.

Alteration of chromosome structure (Fig 15.14)

• Deletions, duplications, inversions, reciprocal translocations.

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