Genetics Notes
Chapter 4 - Sex Determination and Sex-linked Characteristics
Chapter 6 - Pedigree Analysis and Applications

These notes are provided to help direct your study from the textbook. They are not designed to explain all aspects of the material in great detail; that is what class time and the textbook is for. If you were to study only these notes, you would not learn enough genetics to do well in the course.

In the late 1800's and early 1900's, various scientists discovered that
  1. the chromosomes within the nucleus divide longitudinally during cell division
  2. the divided chromosomes were distributed in equal numbers to the daughter cells
  3. the total number of chromosomes remains constant in all cells of an organism except during gamete formation
  4. the chromosome number varies greatly from species to species
  5. in 1903, Sutton and Boveri noted that the transmission of chromosomes from one generation to the next paralleled the transmission of genes from generation to generation
They proposed the Chromosome Theory of Heredity which states that the chromosomes are the carriers of the genes. As there are many more loci/genes in an organism, it follows that a single chromosome has many loci. (pages 52 and 87)

Sex Determination

In dioecious species (separate sexes) there are several means to determine sex. The chromosomes involved in sex determination are called sex chromosomes. All other chromosomes are called autosomal chromosomes or autosomes. Although sex chromosomes provide the most common means of sex determination, it is not the only mechanism.
  1. in bees, males are haploid (N) while females are diploid (2N) (figure 4.6)
  2. sex may be determined by a single allele or multiple alleles as in some wasps
  3. by environmental factors as in some turtles, these have indeterminate genetic sex-determining mechanisms. The temperature at which the eggs are incubated determines the sex of the turtles. In some species, warm nests yield mostly males and cool nests yield mostly females. In other species of turtles this is reversed.
We will limit our discussion to chromosomal sex determining mechanisms as this is most common and is the mechanism seen in mammals.

The autosomes occur in homologous pairs with each chromosome possessing one copy (allele) of each gene. Segregation and reassortment lead to the pattern of inheritance that we have seen so far, which is called Mendelian inheritance. The sex chromosomes may be genetically distinct thus homologous pairs may not exist and this leads to inheritance patterns that are different from autosomal inheritance.

There are four basic types of chromosomal mechanisms
  1. XX-XY (figures 4.4 & 4.5) in which females are homomorphic XX and males are heteromorphic XY (figures 4.1 & 4.5). This is found in mammals including humans and some insects including Drosophila.
    In humans, females have 23 homomorphic pairs and males have 22 homomorphic pairs plus a heteromorphic pair. During meiosis, females produce only one kind of gamete all having one X chromosome. Males produce two kinds of gametes, one with an X and the other with a Y chromosome. Females are homogametic and males are heterogametic.
  2. ZZ-ZW system in which females are heteromorphic ZW and males are homomorphic ZZ. This occurs in birds, some fishes, and moths. It is essentially the opposite of XY in mammals.
  3. XX-XO system in which females have 2 X chromosomes. Males have only 1 X and no additional sex chromosomes. Females have an even number of chromosomes and males have an odd number of chromosomes. This occurs in many species of insects. This was the first sex determining mechanism discovered, and the sex determining chromosome was named the X in 1905. Gametes of males have either an X chromosome or no sex chromosome.
  4. compound chromosome system These can be very complex with multiple numbers of X and Y chromosomes. e.g. in Ascaris incurva, a nematode, there are 26 autosomes, 8 X chromosomes, and 1 Y chromosome Males have 26A + 8X + Y for 35 chromosomes Females have 26A + 16X for 42 chromosomes This type of system is also common in spiders.
Sex determination in the XY system is the most studied because it is found in humans and Drosophila. Does the X chromosome or the Y chromosome determine the sex? It varies from species to species. In Drosophila, the greater the number of X chromosomes relative to the autosomes, the more likely the individual will be female (table 4.1).
phenotypechromosomal complement# of X/# of autosomal sets
normal female XX + 2N autosomes 1.00
normal male XY + 2N autosomes 0.50
metafemale XXX + 2N autosomes 1.50
metamale X + 3N autosomes 0.33
intersex XX + 3N autosomes 0.67

Sex balance theory or genic balance theory states that the X chromosome determines the sex of the individual and that sex is a dosage phenomena, where the ratio of the amount of the X relative to the autosomes determines the sex. In addition, environmental effects can influence the development of the intersex flies.

Further studies have shown that sex is ultimately determined by the locus sex-lethal on the X chromosome, though several other loci on the X chromosome and the autosomes are also needed for sex determination.

The sex balance theory was assumed to apply to other XY systems, including humans. However, cytologic evidence (chromosomal studies) of mice and humans showed that . . .
1) XO were female (Turner) (figure 4.8)
2) XXY were male (klinefelter) (figure 4.9)
which is opposite of what the sex balance theory would predict. All males have at least one Y and all females have no Y's, regardless of the number of X's. The reason is that on the Y chromosome, there is a gene that causes an undifferentiated gonad to become a testis. This gene is called the sex determining region Y (sry) (figure 4.10). Its mode of action is basically to control a number of other genes that effect the development of the sexual characteristics (figure 4.12).

X-linked Inheritance

In animals with XY sex determining mechanism, the X chromosome has many loci, many that have nothing to do with sex as such. The Y is usually smaller and possesses fewer loci that are not the same loci as that on the X chromosome. Thus females that have the same allele at a locus on the X chromosome are homozygous. Different alleles would be heterozygous. Males, because they have only one X, are hemizygous and can have only one allele at a locus. Because of this, one copy of a recessive allele will be expressed in the phenotype in males.

In sex-linked inheritance, crosses are not reciprocal. The X-linked pattern is called the criss-cross pattern of inheritance because fathers pass the trait to daughters who pass it on to sons (figures 4.12, 4.13, and 4.15).

Sex-limited traits are traits that are autosomally inherited, and they are expressed in one sex, but not in the other. Some examples include sexually dimorphic plumage in birds, milk yield in mammals, antlers in deer, beards in humans (figure 5.14).

Sex-influenced traits appear in both sexes but more so in one sex than another. Male pattern baldness in humans is an example. The male hormone testosterone is needed for full expression of baldness. Because of this hormone difference, the allele for baldness behaves as a dominant trait in males (expressed when heterozygous), but behaves as a recessive allele in females (must be homozygous to be expressed) (figure 5.12).

Pedigree Analysis

pleiotropy - a gene that causes or affects the phenotypic development in two or more characteristics. For example, the many symptoms that are seen in individuals who are homozygous for cystic fibrosis - one trait is the build-up of thick mucus in the lungs of affected individuals and a second trait is the abnormal development of the vas deferens in males, which often leads to sterility.

penetrance - an allele that produces the same effect in every individual of the proper genotype is said to have complete penetrance. If this is not the case, the allele is said to be incompletely penetrant )page 67).
                   # of individuals with correct phenotype
    % penetrant = ----------------------------------------------------
                   # of individuals with genotype coding for phenotype
Most alleles show complete penetrance. Here are some examples of alleles that do not.
1) the autosomal dominant allele that causes retinoblastoma
2) the autosomal dominant allele that causes polydactyly
3) the sex-linked dominant allele that causes rickets
4) the autosomal recessive allele that causes eyelessness in Drosophila

expressivity - once a gene is expressed, it may have different degrees of expression (page 67). examples
  1. eyeless in Drosophila. If it penetrates (85%) the phenotype can range from totally eyeless to eyes barely reduced.
  2. polydactyly in humans. If it penetrates, it can range from one extra finger or toe to several extra fingers or toes.
We can now apply what we know about X-linked and autosomal inheritance to determine the inheritance pattern of human traits (figure 6.2).
  1. We must use pedigree analysis because obviously we cannot do the appropriate test crosses to determine inheritance pattern. This often leads us into the situation where we can eliminate some patterns and are left with a couple of possible patterns.
  2. Many times, we do not have enough progeny to make strong statistically valid statements about the mode of inheritance.
  3. We must be concerned with the certainty of paternity. In many studies in the U.S. and Europe, 15-25% of children do not have the father of record.
To do pedigree analysis, we must start with a family tree (figures 6.2 & 6.3 for definitions of symbols).

Four Basic Patterns of Inheritance

Autosomal dominant inheritance -- (figure 6.5)
  1. If the trait is rare, most matings are between heterozygotes (affected) and homozygous (unaffected) recessives, which leads to predominantly 1:1 phenotypic ratios for all children, regardless of sex
  2. the dominant phenotype should appear in every generation, unless there is reduced penetrance
Autosomal recessive inheritance -- (figure 6.4)
  1. generations are often, but not always, skipped
  2. there should be equal distribution among the sexes
  3. if both parents are affected, all children will be affected
  4. often found in consanguineous marriages
  5. most affected children have normal parents
Sex-linked dominance -- (figure 6.9)
  1. no generations are skipped
  2. affected males must come from affected mothers
  3. all the daughters, but none of the sons, of an affected father are affected
  4. approximately half of an affected female's sons and daughters are affected
Sex-linked recessive -- (figures 6.7 & 6.9)
  1. males are most affected
  2. affected males have carrier mothers, who are known to have affected brothers, fathers, or maternal uncles
  3. affected females come from affected fathers and carrier mothers
  4. affected female's sons must be affected
  5. approximately half the sons of carrier females should be affected

The stainable material in a chromosome is called chromatin. In a G1 stage-chromosome, it consists of a single strand of DNA, plus several types of protein. There are two such types of chromatin.
  1. euchromatin is uncoiled or uncondensed during interphase
  2. heterochromatin remains coiled or condensed during interphase and is replicated late during the S phase.
There are two kinds of heterochromatin.
  1. facultative heterochromatin - this heterochromatin may revert to euchromatin depending upon the physiological or developmental conditions of the cell. An example of this is X-inactivation due to the formation of a Barr-body (figure 4.16).
  2. constitutive heterochromatin - is permanently condensed and never euchromatic. The centromeric region is constitutive heterochromatin, but there may be other regions as well.
In males, the single X chromosome is euchromatic. In females, one of the two X chromosomes becomes condensed heterochromatin on the 16th day of embryonic development. In the interphase nucleus, this appears as a dark spot near the edge of the nucleus.

A person will have n-1 Barr bodies where n equals the number of X chromosomes (table 4.2). Thus. . . The result of X-inactivation is to produce a mosaic of phenotypes within females that are heterozygous at an X-linked locus. The inactivated X remains inactivated through all subsequent mitotic events within that cell line.

In human beings, females can be heterozygous for the enzyme glucose-6-phosphate dehydrogenase. Skin cells taken from these individuals can be grown in tissue culture, where each cell grows into a cell line that expresses only one form (allele) of glucose-6-phosphate dehydrogenase. This also occurs in cats, where the locus for coat color is found on the X chromosomes. Males, because they are hemizygous, are either black or orange. Females that are heterozygous the black and tan alleles produce a calico coat color because of random X-inactivation during embryonic development (figure 4.17). Males that are calico, which are quite rare, always turn out to be XXY and are thus heterozygous at the coat color locus and produce the same pattern as females.

Last update on 31 January 2007
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