Organisms have two kinds of chromosomes in the nuclei of their cells:
1. sex chromosomes -- a single homologous pair -- determine the gender of the individual.
2. autosomes -- all other homologous pairs -- not involved in sex determination.
Humans have 23 homologous pairs of chromosomes -- 1 pair are sex chromosomes and the remaining 22 pairs are autosomes.
sex chromosomes -- one pair of homologues that determine the gender (male or female) of the organisms -- unlike other homologous chromosomes which tend to be the same in terms of length, shape and gene sequence, sex chromosomes differ from one another considerably.
a. X-chromosome -- large chromosome that in mammals specifies the female gender.
b. Y-chromosome -- small chromosome that specifies the male gender -- many fewer genes than X-chromosome.
Individuals having two X-chromosomes are females, while XY individuals are male -- female gametes (ova) all contain an X-chromosome, while half of a male’s gametes (sperm) contain an X-chromosome and the other half contain a Y-chromosome.
Figure 11.3.
Now that we have a basic understanding of genetics and the nature of the gene, I want to interject some relevancy by discussing human genetic disorders.
A number of very serious human health disorders have a genetic basis -- they are inherited. How do we know if a trait or disorder in humans has genetic basis?
It is difficult/unethical to do breeding experiments with humans -- geneticists use pedigree analysis -- pedigree is a diagram illustrating parent-offspring relationships -- by noting the appearance of traits and disorders in the pedigrees, patterns of inheritance could be found and these can be used to infer something about the genetic nature of the disorder.
Question: how did these disorders arise and why are they still around?
Answer: they arose by mutation and mutation will keep them around.
Mutation: "heritable changes in the genetic material (DNA)" -- occur during meiosis and gametogenesis -- important to evolution because it is the source of all new genetic variation and evolution cannot occur without genetic variation.
Mutations occur randomly -- almost always harmful.
Two general kinds of mutations:
1. gene (point) mutations -- changes in DNA base sequences -- results in new alleles at genes.
2. chromosomal mutations -- changes in the number or structure of chromosomes.
Mutations may be spontaneous and occur for reasons that are still unknown or they may be induced.
Agents that cause or increase the rate at which mutations occur are called mutagens -- e.g. X-rays and UV; various chemicals -- many mutagens have also been shown to be carcinogens (cancer causing agents).
Rates of particular mutations vary, but they are generally very rare -- e.g. 10-5 to 10-8 per gamete -- chances of mutant gamete taking place in fertilization is thus very low -- does happen.
Important point: even if we could prevent the reproduction of people known to carry deleterious mutant alleles, we could not get rid of these alleles because mutations are recurrent and these alleles are constantly being re-introduced into our population.
Let's look at some human genetic disorders.
1908 -- English physician Garrod first suggested a relationship between certain metabolic disorders and genetics -- "inborn errors of metabolism" -- studied the phenylalanine metabolic pathway -- found that faulty enzymes produced by recessive alleles were responsible for several disorders (e.g. PKU, albinism).
Many genetic disorders are produced by recessive alleles at single genes: albinism, hemophilia, Tay-Sachs disease, cystic fibrosis, Huntington's chorea, some forms of muscular dystrophy, and many others.
Other disorders are caused by chromosomal mutations.
1. Turner's Syndrome -- monosomy of sex chromosomes (XO) -- 1/10,000 births in U.S. -- many more probably lost as miscarriages -- females with short stature, webbed neck, undeveloped sex organs and are sterile.
2. Klinefelter's Syndrome -- trisomy of sex chromosomes (XXY) -- 1/800 births in U.S. -- often not detected until puberty -- males with sparse body hair, some breast development, small penis and testes, usually mentally retarded and sterile.
3. Supermale Syndrome -- trisomy of sex chromosomes (XYY) -- 1/1,000 births in U.S. -- tall stature, severe acne, some retardation, fertile -- 20X more frequent in prison pop. than general pop -- suggested that these individuals were more aggressive and prone to violent crime -- used as legal defense -- found to be no more aggressive than XY males -- get caught more often because they are below average intelligence.
4. Down's Syndrome -- trisomy of chromosome #21 -- 1/700 births in U.S. -- severe retardation, deformities, leukemia, heart and respiratory trouble -- reduced survival -- incidence related to age of parents:
Mother's Age Rate 16-24 1/1700 35-39 1/250 45+ 1/25
often attributed to mother and "old eggs" -- recent research has attributed 20-25% of cases to father's age.
Now, besides determining sex, sex chromosomes carry genes that have nothing to do with sex -- in fact, some genes only exist on one but not both of the sex chromosomes -- genes of this type are said to be sex-linked.
Sex-linked genes:
1. X-linked genes are found only on the X chromosome and are not on the Y -- 120 or so traits in humans known to be X-linked.
2. Y-linked genes are found only on the Y chromosome and not on the X -- not many Y-linked genes known.
X-linked traits in humans: red-green colorblindness, hemophilia, muscular dystrophy, myopia, juvenile glaucoma are all traits that are controlled by recessive alleles for genes found on the X (but not the Y) chromosome in humans.
Several things to note about X-linked traits:
1. recessive alleles will be expressed in males even in a single dose -- traits most often seen in males.
2. males usually obtain allele from their mother, who, in turn, got it from her father -- disease tends to "skip generations."
3. females are usually "carriers" (heterozygotes) of these disorder and have normal phenotypes.
Let's look at sex-linked inheritance through the example of hemophilia -- disorder caused by a recessive allele at an X-linked gene -- allele produces a nonfunctional enzyme that causes blood not to clot -- smallest cut or bruise can be life threatening -- "bleeder's disease" -- often detected at birth by bleeding from umbilical stump or from circumcision.
Treated today by injections of functional enzyme purified from human blood serum -- daily injections costing about $6,000/year -- also being produced by genetically engineered bacteria.
In the U.S. there are about 20,000 hemophiliacs -- nearly all are males.
Consider a male hemophiliac who marries a normal woman -- in the F1, all sons will be normal (X-chrom. from mom), while all daughters will be carriers (heterozygotes, normal clotting) -- no hemophilia this generation -- now, daughters marry normal males produce next generation -- notice that the ratio of normal blood clotting is 3:1 -- notice further that of the 1/4 of the offspring that can be expected to have hemophilia, all are males -- 1/2 of the females are carriers.
See Diagram:
Is it possible to have a females with hemophilia? Yes -- marriage of a hemophiliac male (rare) with a carrier female (still rare) will produce daughters that are hemophiliacs -- a very rare event.
Queen Victoria -- most famous carrier of hemophilia -- no history in her family and is assumed that she received the allele by mutation in one of her parents -- at one point, 18 of her 69 descendents had the hemophilia allele -- had 2 daughters that were carriers and 1 son that was a hemophiliac -- allele passed to various royal families in Europe -- granddaughter (carrier) married Nicholas II, the last czar of Russia -- had hemophiliac son, Crown Prince Alexis -- Rasputin recruited to cure the boy -- executed along with rest of the family during the Russian revolution.
Figure 11.2 shows part of Queen Victoria's family pedigree.
Next Time: EXAM I