Presentation on theme: "The Chromosomal Basis of Inheritance Chapter 15. New knowledge confirms Mendel’s principles… ► 1890: Cell biologists understand process of meiosis. ►"— Presentation transcript:
The Chromosomal Basis of Inheritance Chapter 15
New knowledge confirms Mendel’s principles… ► 1890: Cell biologists understand process of meiosis. ► 1902: Confirmed that chromosomes are paired in diploid cells, and that they separate in meiosis. ► Biologists develop the chromosome theory of inheritance: ► Mendel’s “factors”, now “genes” are located on chromosomes. ► Chromosomes segregate and independently assort during gamete formation. ► Important work started in 1910 by Thomas Hunt Morgan from Columbia University who performed experiments with the fruit fly Drosophila melanogaster; These flies: ► Are easily cultured in the laboratory (live in small jars; can be anesthetized). ► Are prolific breeders (100’s of eggs laid). ► Have a short generation time (10 days). ► Have only four pairs of chromosomes which are easily seen with a microscope.
An exception to Mendel’s rule… ► Linked genes -- Genes located on the same chromosome, which do not indepedently assort and tend to be inherited together. ► B = normal body color b = black body ► W = normal wing shape w = vestigial wing ► BbWw x bbww 1 norm/norm : 1 norm/vest : 1 black/norm : 1 black/vest (expected) ► BbWw x bbww 5 norm/norm : 1 norm/vest : 1 black/norm : 5 black/vest (observed) ► Sturtevant hypothesized that probability of crossing over between two genes is directly proportional to the distance between them. ► He used recombination frequencies between genes to assign them a linear position on a chromosome map. ► One map unit = 1% recombination frequency; genes farthest apart have highest recombination frequency.
Discovery of a Sex-Linked Gene ► Sex-linked genes -- Genes located on sex chromosomes, commonly applied only to genes on the X chromosome. ► Morgan discovered a male fly with white eyes instead of the wild-type red eyes. Morgan mated this mutant white-eyed male with a red-eyed female. ► w = white-eye allele ► w+ = red-eye or wild-type allele ► P generation: X w+ X w+ x X w Y ► F1 generation: X w+ X w and X w+ Y (all red-eyed) ► F2 generation: X w+ X w+ and X w+ X w (all females red-eyed) ► X w+ Y and X w Y (half males red; half males white) ► Morgan’s conclusions: ► If eye color is located only on the X chromosome, then females (XX) carry two copies of the gene, while males (XY) have only one. ► Since the mutant allele is recessive, a white-eyed female must have that allele on both X chromosomes (impossible in this case). ► A white-eyed male has no wild-type allele to mask the recessive mutant allele, so a single copy results in white eyes.
Sex-Linked Disorders in Humans ► Color blindness, Duchenne muscular dystrophy, hemophilia. ► Human X-chromosome is much larger than the Y; more genes on the X, many without a homologous loci on the Y. ► Fathers pass X-linked alleles to only and all of their daughters. ► Males receive their X chromosome only from their mothers. ► Fathers cannot pass X-linked traits to their sons. ► Mothers can pass X-linked alleles to both sons and daughters. ► A female that is heterozygous for the trait can be a carrier, but not show the recessive trait herself; far more males than females have sex-linked disorders. ► Males are said to be hemizygous (having only one copy of a gene in a diploid organism).
Sex-Limited/Sex-Influenced Traits ► Autosomal traits which affect one gender more than the other. ► A dominant gene causes a rare type of uterine cancer, but only affects women. ► A form of baldness also caused by a dominant gene usually only affects men because of hormone levels.
X Inactivation in Females ► In female mammals, most diploid cells have only one fully functional X chromosome; one of the 2 chromosomes is inactivated during embryonic development. ► Inactive X chromosome condenses into an object called a Barr body; most Barr body genes are not expressed. ► Barr bodies are highly methylated compared to active DNA; Methyl groups (-CH 3 ) attach to cytosine. ► Female mammals are a mosaic of two types of cells, one with an active X from the father and one with an active X from the mother; inactivation appears to happen randomly. ► Examples of this type of mosaicism are coloration in calico cats.
Genetic Disorders: Alterations of Chromosome Number ► Aneuploidy -- having an abnormal number of certain chromosomes. ► Three copies of a chromosome is called “trisomy” (Down’s Syndrome, or Trisomy 21); missing a chromosome is called “monosomy” (Turner’s Syndrome). ► Polyploidy -- more than two complete chromosome sets. ► Triploidy means three haploid chromosome sets (3N); may be produced by fertilization of an abnormal diploid egg. ► Tetraploidy means four haploid chromosome sets (4N); may result by mitosis without cytokinesis. ► Polyploidy is common in plants, but occurs rarely in animals. ► Nondisjunction -- error in meiosis when homologous chromosomes or sister chromatids fail to separate into different gametes.
Genetic Disorders: Alterations of Chromosome Number(cont) ► Aneuploidy usually prevents normal embryonic development and often results in spontaneous abortion. ► Some types cause less severe problems. ► Down syndrome (1 in 700 live births in U.S.); characteristic facial features, short stature, heart defects, mental retardation. ► Correlates with maternal age; time lag prior to completion of meiosis at ovulation? ► Rarer disorders are Patau syndrome (trisomy 13) and Edwards syndrome (trisomy 18); incompatable with life. ► Sex chromosome aneuploidy: ► Klinefelter Syndrome (usually XXY); sterile males with feminine body characteristics. ► Extra Y (or “super-male”, XYY); taller males with higher testosterone production. ► Turner Syndrome (XO); only known viable human monosomy; short stature; sexual characteristics fail to develop; sterile.
Genetic Disorders: Alterations of Chromosome Structure ► Chromosome breakage can alter chromosome structure in four ways: ► 1. Deletion: loss of a fragment of chromosome. ► 2. Duplication: lost fragment attaches to a homologous chromosome, repeating a sequence. ► 3. Translocation: lost fragment joins to a nonhomologous chromosome. ► 4. Inversion: lost fragment reattaches to the original chromosome in reverse. ► These errors usually happen during crossing-over.
Genetic Disorders: Alterations of Chromosome Structure(cont) ► Cri du chat syndrome; deletion on chromosome; mental retardation, unusual facial features, and cat’s cry. ► Chronic myelogenous leukemia (CML); portion of chromosome 22 switches places with fragment from chromosome 9. ► Some cases of Down syndrome: the third chromosome 21 translocates to chromosome 15. ► Prader-Willi syndrome; deletion from the paternal chromosome 15; mental retardation, obesity, short stature. ► Angelman syndrome; same deletion from the maternal chromosome 15; uncontrollable spontaneous laughter, jerky movements, and other mental symptoms. ► Genomic imprinting -- changes in chromosomes inherited from males and females; certain genes expressed differently depending upon whether inherited from the ovum or from the sperm cell.
Genetic Disorders: Alterations of Chromosome Structure(cont) ► Fragile X syndrome (1 in 1500 males; 1 in 2500 females); most common genetic cause of mental retardation. ► Caused by triplet repeat (CGG); repeated up to 50 times on the tip of a normal X chromosome; repeated more than 200 times in a fragile X chromosome. ► Syndrome more likely to appear if the abnormal X chromosome is inherited from the mother; chromosomes in ova are more likely to acquire new CGG triplets than chromosomes in sperm. ► Maternal imprinting explains why fragile-X disorder is more common in males. Males (XY) inherit the fragile X chromosome only from their mothers. ► Heterozygous carrier females are usually only mildly retarded.