CHAPTER 15

THE CHROMOSOMAL BASIS OF INHERITANCE

 

A. Relating Mendelism to Chromosomes

1. Mendelian inheritance has its physical basis in the behavior of chromosomes during sexual life cycles

·        Around 1900, cytologists and geneticists began to see parallels between the behavior of chromosomes and the behavior of Mendel’s factors.

·        Chromosomes and genes are both present in pairs in diploid cells.

·        Homologous chromosomes separate and alleles segregate during meiosis.

·        Fertilization restores the paired condition for both chromosomes and genes.

·        Around 1902, Walter Sutton, Theodor Boveri, and others noted these parallels and a chromosome theory of inheritance began to take form.

 

2. Morgan traced a gene to a specific chromosome

·        Thomas Hunt Morgan was the first to associate a specific gene with a specific chromosome in the early 20th century.

·        Like Mendel, Morgan made an insightful choice as an experimental animal, Drosophila melanogaster, a fruit fly species that eats fungi on fruit.

·        Fruit flies are prolific breeders and have a generation time of two weeks.

·        Fruit flies have three pairs of autosomes and a pair of sex chromosomes (XX in females, XY in males).

·        Morgan spent a year looking for variant individuals among the flies he was breeding.

·        He discovered a single male fly with white eyes instead of the usual red.

·        The normal character phenotype is the wild type.

·        Alternative traits are mutant phenotypes.

·        When Morgan crossed his white-eyed male with a red-eyed female, all the F1 offspring had red eyes,

·        The red allele appeared dominant to the white allele.

·        Crosses between the F1 offspring produced the classic 3:1 phenotypic ratio in the F2 offspring.

·        Surprisingly, the white-eyed trait appeared only in males.

·        All the females and half the males had red eyes.

·        Morgan concluded that a fly’s eye color was linked to its sex.

·        Morgan deduced that the gene with the white-eyed mutation is on the X chromosome alone, a sex-linked gene.

·        Females (XX) may have two red-eyed alleles and have red eyes or may be heterozygous and have red eyes.

 

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

 

4. Independent assortment of chromosomes and crossing over produce genetic recombinants

 

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

 

B. Sex Chromosomes

1. The chromosomal basis of sex varies with the organism

·        Although the anatomical and physiological differences between women and men are numerous, the chromosomal basis of sex is rather simple.

·        In human and other mammals, there are two varieties of sex chromosomes, X and Y.

·        An individual who inherits two X chromosomes usually develops as a female.

·        An individual who inherits an X and a Y chromosome usually develops as a male.

·        This X-Y system of mammals is not the only chromosomal mechanism of determining sex.

·        Other options include the X-0 system, the Z-W system, and the haplo-diploid system.

·        In the X-Y system, Y and X chromosomes behave as homologous chromosomes during meiosis.

·        In reality, they are only partially homologous and rarely undergo crossing over.

·        In both testes (XY) and ovaries (XX), the two sex chromosomes segregate during meiosis and each gamete receives one.

·        Each egg receives an X chromosome.

·        Half the sperm receive an X chromosome and half receive a Y chromosome.

·        Because of this, each conception has about a fifty-fifty chance of producing a particular sex.

·        In humans, the anatomical signs of sex first appear when the embryo is about two months old.

·        In individuals with the SRY gene (sex-determining region of the Y chromosome), the generic embryonic gonads are modified into testes.

·        Activity of the SRY gene triggers a cascade of biochemical, physiological, and anatomical features because it regulates many other genes.

·        In addition, other genes on the Y chromosome are necessary for the production of functional sperm.

·        In individuals lacking the SRY gene, the generic embryonic gonads develop into ovaries.

 

2. Sex-linked genes have unique patterns of inheritance

·        In addition to their role in determining sex, the sex chromosomes, especially the X chromosome, have genes for many characters unrelated to sex.

·        These sex-linked genes follow the same pattern of inheritance as the white-eye locus in Drosophila.

·        If a sex-linked trait is due to a recessive allele, a female will have this phenotype only if homozygous.

·        Heterozygous females will be carriers.

·        Because males have only one X chromosome (hemizygous), any male receiving the recessive allele from his mother will express the trait.

·        The chance of a female inheriting a double dose of the mutant allele is much less than the chance of a male inheriting a single dose.

·        Therefore, males are far more likely to inherit sex-linked recessive disorders than are females.

·        Several serious human disorders are sex-linked.

·        Duchenne muscular dystrophy affects one in 3,500 males born in the United States.

·        Affected individuals rarely live past their early 20s.

·        This disorder is due to the absence of an X-linked gene for a key muscle protein, called dystrophin.

·        The disease is characterized by a progressive weakening of the muscles and a loss of coordination.

·        Hemophilia is a sex-linked recessive trait defined by the absence of one or more clotting factors.

·        These proteins normally slow and then stop bleeding.

·        Individuals with hemophilia have prolonged bleeding because a firm clot forms slowly.

·        Bleeding in muscles and joints can be painful and lead to serious damage.

·        Individuals can be treated with intravenous injections of the missing protein.

 

C. Errors and Exceptions in Chromosomal Inheritance

·        Sex-linked traits are not the only notable deviation from the inheritance patterns observed by Mendel.

·        Also, gene mutations are not the only kind of changes to the genome that can affect phenotype.

·        Major chromosomal aberrations and their consequences produce exceptions to standard chromosome theory.

·        In addition, two types of normal inheritance also deviate from the standard pattern.

 

1. Alterations of chromosome number or structure cause some genetic disorders

·        Nondisjunction occurs when problems with the meiotic spindle cause errors in daughter cells.

·        This may occur if tetrad chromosomes do not separate properly during meiosis I.

·        Alternatively, sister chromatids may fail to separate during meiosis II.

·        As a consequence of nondisjunction, some gametes receive two of the same type of chromosome and another gamete receives no copy.

·        Offspring results from fertilization of a normal gamete with one after nondisjunction will have an abnormal chromosome number or aneuploidy.

·        Trisomic cells have three copies of a particular chromosome type and have 2n + 1 total chromosomes.

·        Monosomic cells have only one copy of a particular chromosome type and have 2n - 1 chromosomes.

·        If the organism survives, aneuploidy typically leads to a distinct phenotype.

·        Aneuploidy can also occur during failures of the mitotic spindle.

·        If aneuploidy happens early in development, this condition will be passed along by mitosis to a large number of cells.

·        This is likely to have a substantial effect on the organism.

·        Organisms with more than two complete sets of chromosomes, have undergone polypoidy.

·        This may occur when a normal gamete fertilizes another gamete in which there has been nondisjunction of all its chromosomes.

·        The resulting zygote would be triploid (3n).

·        Alternatively, if a 2n zygote failed to divide after replicating its chromosomes, a tetraploid (4n) embryo would result from subsequent successful cycles of mitosis.

 

·        Polyploidy is relatively common among plants and much less common among animals.

·        Breakage of a chromosome can lead to four types of changes in chromosome structure.

·        A deletion occurs when a chromosome fragment lacking a centromere is lost during cell division.

·        This chromosome will be missing certain genes.

·        A duplication occurs when a fragment becomes attached as an extra segment to a sister chromatid.

·        An inversion occurs when a chromosomal fragment reattaches to the original chromosome but in the reverse orientation.

·        In translocation, a chromosomal fragment joins a nonhomologous chromosome.

·        Some translocations are reciprocal, others are not.

·        Certain aneuploid conditions upset the balance less, leading to survival to birth and beyond.

·        These individuals have a set of symptoms — a syndrome — characteristic of the type of aneuploidy.

·        One aneuploid condition, Down syndrome, is due to three copies of chromosome 21.

·        It affects one in 700 children born in the United States.

·        Although chromosome 21 is the smallest human chromosome, it severely alters an individual’s phenotype in specific ways.

·        Most cases of Down syndrome result from nondisjunction during gamete production in one parent.

·        The frequency of Down syndrome correlates with the age of the mother.

·        This may be linked to some age-dependent abnormality in the spindle checkpoint during meiosis I, leading to nondisjunction.

·        Trisomies of other chromosomes also increase in incidence with maternal age, but it is rare for infants with these autosomal trisomies to survive for long.

·        Nondisjunction of sex chromosomes produces a variety of aneuploid conditions in humans.

·        Unlike autosomes, this aneuploidy upsets the genetic balance less severely.

·        This may be because the Y chromosome contains relatively few genes.

·        Also, extra copies of the X chromosome become inactivated as Barr bodies in somatic cells.

·        Klinefelter’s syndrome, an XXY male, occurs once in every 2000 live births.

·        These individuals have male sex organs, but are sterile.

·        There may be feminine characteristics.

·        Their intelligence is normal.

·        Males with an extra Y chromosome (XYY) tend to somewhat taller than average.

·        Trisomy X (XXX), which occurs once in every 2000 live births, produces healthy females.

·        Monosomy X or Turner’s syndrome (X0), which occurs once in every 5000 births, produces phenotypic, but immature females.

·        Some individuals with Down syndrome have the normal number of chromosomes but have all or part of a third chromosome 21 attached to another chromosome by translocation.

 

2. The phenotypic effects of some mammalian genes depend on whether they were inherited from the mother or the father (imprinting)

 

3. Extranuclear genes exhibit a non-Mendelian pattern of inheritance

·        Not all of a eukaryote cell’s genes are located in the nucleus.

·        Extranuclear genes are found on small circles of DNA in mitochondria and chloroplasts.

·        These organelles reproduce themselves.

·        Their cytoplasmic genes do not display Mendelian inheritance.

·        They are not distributed to offspring during meiosis.