Chapter 15: The Chromosomal Basis for Inheritance

• One of biology’s most important concepts, the chromosome theory of inheritance, states that:

– Genes have specific locations on chromosomes.

– The behavior of chromosomes during meiosis and fertilization accounts for inheritance patterns

– We can see the chromosomal basis of Mendel’s principles by following the fates of two genes during meiosis and fertilization in pea plants

Figure 15.2 The chromosomal basis of Mendel’s laws

Morgan traced a gene to a specific chromosome

• Experimental organism: Drosophila Melanogaster (fruit fly).

• Easy to raise, prolific breeders, easily identified traits, four chromosomes pairs.

– 3 pairs autosomes and one pair sex chromosomes.

Morgan traced a gene to a specific chromosome

• After discovering a white eyed male fly, he mated with with a red-eyed female.

• All the F₁ offspring had red eyes.

• The F₂ offspring had both red and white eyes, with a 3:1 ratio of red to white.

• But, there is a twist to the story.

• All the F₂ females had red eyes, while half the F₂ males had red eyes and half had white eyes.

• Somehow, a fly’s eye color was linked to its sex.

Sex Linked Genes

• Morgan’s made hypothesis: The gene for red v. white eye color is found on the X chromosome.

• Thus, females, XX have two alleles of the gene, while males, XY have only one allele.

• A female will only have white eyes if she receives two recessive alleles. A male has no back-up copy, so if he receives a recessive allele, he will have white eyes.

Figure 15.4

Linked Genes

• Genes found on the same chromosome are more likely to be inherited together, and are therefore ‘linked’.

• In another experiment, Morgan examined the effect gene linkage and inheritance

Independent assortment of chromosomes: recombination of linked genes. (p. 278)

Recombination of Linked Genes (p. 278)

How does linkage influence inheritance?

• Wild type flies have gray bodies and normal wings.

• Flies can also have have black bodies and ‘vestigial’ wings (very small wings), both are recessive traits.

• The alleles are represented with the following symbols: b⁺ = gray body; b = black body; vg⁺=normal wings; vg = vestigial wings.

• Neither gene is sex-linked.

How does linkage influence inheritance?

• Morgan mated true breeding wild-type flies (b⁺b⁺ vg⁺vg⁺) with true breeding black, vestigial-winged ones (bb vg vg).

• The F₁ generation were all wild type.

• Morgan then did a test-cross.

• He crossed the F₁ generation with true breeding black, vestigial-winged flies (bb vg vg).

• The offspring predicted would be a 1:1:1:1 ratio of wild type; gray w/ vestigial wings; black w/ normal wings; black w/ vestigial wings.

• However, the observed phenotype was showed the two parental phenotypes, wild type and black w/ vestigial wings at a 1:1 ratio, and a smaller portion of recombinant offspring.

Fig.15.4 Are the genes for body color and wing size in fruit flies located on the same chromosome or different chromosomes?

Fig. 15.6 Chromosomal basis for recombination of linked genes.

Linkage Mapping (Fig. 15.7)

• The frequency of recombination can be used to determine the distance between two loci, and the relative locations of genes on a chromosome.

• The distance between genes is expressed in map units.

– One map unit is equivalent to a 1% recombination frequency.

Fig. 15.8 A partial genetic map of a Drosophila chromosome

Cytological Mapping

• Cytological maps of chromosomes locate genes with respect to chromosomal feature, such as stained bands that can be seen in the microscope.

• http://www.accessexcellence.org/RC/VL/GG/fish.html

• The genetic basis of sex determination is not yet fully understood but one gene, SRY, on the Y chromosome plays a crucial role:

– This gene triggers testicular development

– In its absence ovaries develop rather than testes

• Other genes on the Y chromosome are also necessary for normal sperm production

Fig. 15.9 Some chromosomal systems of sex determination.

Sex Linked Genes

• Any gene on a sex chromosome is sex-linked

• Sex chromosomes contain both genes that determine sex and genes that are unrelated to sex determination

• The Y chromosome is 1/3 the size and carries 1/100 of the genes found on the X chromosome

• Most sex-linked genes unrelated to sex determination are found on the X chromosome

Figure 15.10 The transmission of sex-linked recessive traits

Sex-linked genes have different patterns of inheritance than autosomal genes because females are diploid while males are only haploid. Males do not get back-up copy.

Sex Linked Genes – X versus Y

• Thus if a gene unrelated to sex determination is present on the X chromosome then it is unlikely to have a twin on the Y

• If this gene is recessive it will still be expressed in the male as there is no twin to counter it

• The female, having two X’s needs both to be recessive before the condition would be displayed

Sex Linked Disorders in Humans

• A number of human conditions result from sex-linked (X-linked) recessive alleles that are expressed more commonly in males than females

– Red-Green color blindness

• Involves several X-linked genes

• Normal color vision includes about 150 colors, but red-green color blindness involves fewer than 25

– Hemophilia – missing the blood clotting factor VIII.

– Duchene Muscular Dystrophy – the gene for dystrophin is mutated. Muscular wasting and severely shortened lifespan.

X-Inactivation in Female Mammals

• Females inherit two X chromosomes, however one X cell in each cell becomes inactivated.

• The inactive X condenses into a Barr body.

• Inactivation occurs randomly, early in embryonic development.

• Females consist of a mosaic of two types of cells.

Figure 15.11 X inactivation and the tortoiseshell cat

Calico cat

Errors in Chromosome Number

• Occasionally there are errors in meiosis called “non-disjunction”.

• The members of a pair of homologous chromosomes to not move apart properly in Meiosis I, OR

• The sister chromatids do not split in meiosis II.

Figure 15.12 Meiotic nondisjunction

Errors in Chromosome Number

• If the aberrant gametes unite with a normal one a fertilization, the offspring will have an abnormal chromosome number known as aneuploidy.

– Trisomy = 2n + 1

– Monosomy = 2n - 1

• Occasional, an organism can have more the two complete chromosome sets

– Polyploidy

Figure 15.13 A tetraploid mammal?

Alterations in Chromosome Structure

• A deletion occurs when a segment of a chromosome is lost during cell division.

• A duplication occurs if a segment of a chromosome becomes duplicated in that chromosome.

• An inversion is when a segment of a chromosomes becomes inverted so that it is in opposite orientation to it’s normal position.

• A translocation is when a portion of one chromosome become fused to another chromosome.

Fig. 15.14 Alterations of chromosome structure

Chromosomal Alterations in Humans

• Most cases of aneuploidy result in early embryonic death because the consequences are so severe.

• Incidence of aneuploidy increases with maternal age.

Down Syndrome

• Incidence is 1/700 birth.

• A result of extra chromosome 21 or a translocation of a portion of chromosome 21 onto chromosome 14.

• Characteristic facial feature, short stature, mental retardation, heart defects, susceptibility to respiratory infections, increased incidence of leukemia and Alzheimer's disease.

Down Syndrome

Nondisjunction of sex chromosomes

• Klinefelter syndrome, XXY; 1/2000 births

– Male sex organs, but testis small undeveloped, usually sterile.May have breast enlargement. Intelligence within normal range.

• Turner syndrome XO; 1/5000 births

– Sex organs do not mature, sterile. May have webbed neck. Normal intelligence .

• XYY, no defined syndrome. May be taller.

• XXX virtually indistinguishable from XX.

Klinefelter syndrome

XYY karyotype

Alterations in Chromosome Structure in Humans

• Cri du chat

– A portion of chromosome 5 is deleted.

– The baby has a small head, an unusual cry that sounds like a cat mewing, abnormal facial features and usually dies in infancy.

• Chromic myelogenous leukemia

– A portion of chromosome 22 is swapped with a piece of the tip of chromosome 9.

Figure 15.16 Translocation associated with chronic myelogenous leukemia.

Genomic Imprinting

• The phenotypic effects of some mammalian genes depend on whether they were inherited from the mother or the father.

• A deletion of chromosome 15 can cause two distinct syndromes, depending on which parent it is inherited from.

– If the abnormal chromosome comes from the father, the child has Prader-Willi syndrome.

• Compulsive eating, short stature, mental retardation.

– If the abnormal chromosome comes from the mother, the child has Angelman syndrome.

• Uncontrollable laughter, jerky movements, other motor and mental difficulties.

Chapter 15: The Chromosomal Basis for Inheritance

• One of biology’s most important concepts, the chromosome theory of inheritance, states that:

– Genes have specific locations on chromosomes.

– The behavior of chromosomes during meiosis and fertilization accounts for inheritance patterns

– We can see the chromosomal basis of Mendel’s principles by following the fates of two genes during meiosis and fertilization in pea plants

Figure 15.2 The chromosomal basis of Mendel’s laws

Morgan traced a gene to a specific chromosome

• Experimental organism: Drosophila Melanogaster (fruit fly).

• Easy to raise, prolific breeders, easily identified traits, four chromosomes pairs.

– 3 pairs autosomes and one pair sex chromosomes.

Morgan traced a gene to a specific chromosome

• After discovering a white eyed male fly, he mated with with a red-eyed female.

• All the F1 offspring had red eyes.

• The F2 offspring had both red and white eyes, with a 3:1 ratio of red to white.

• But, there is a twist to the story.

• All the F2 females had red eyes, while half the F2 males had red eyes and half had white eyes.

• Somehow, a fly’s eye color was linked to its sex.

Sex Linked Genes

• Morgan’s made hypothesis: The gene for red v. white eye color is found on the X chromosome.

• Thus, females, XX have two alleles of the gene, while males, XY have only one allele.

• A female will only have white eyes if she receives two recessive alleles. A male has no back-up copy, so if he receives a recessive allele, he will have white eyes.

Linked Genes

• Genes found on the same chromosome are more likely to be inherited together, and are therefore ‘linked’.

• In another experiment, Morgan examined the effect gene linkage and inheritance

Independent assortment of chromosomes: recombination of linked genes. (p. 278)

Recombination of Linked Genes (p. 278)

How does linkage influence inheritance?

• Wild type flies have gray bodies and normal wings.

• Flies can also have have black bodies and ‘vestigial’ wings (very small wings), both are recessive traits.

• The alleles are represented with the following symbols: b+ = gray body; b = black body; vg+=normal wings; vg = vestigial wings.

• Neither gene is sex-linked.

How does linkage influence inheritance?

• Morgan mated true breeding wild-type flies (b+b+ vg+vg+) with true breeding black, vestigial-winged ones (bb vg vg).

• The F1 generation were all wild type.

• Morgan then did a test-cross.

• He crossed the F1 generation with true breeding black, vestigial-winged flies (bb vg vg).

• The offspring predicted would be a 1:1:1:1 ratio of wild type; gray w/ vestigial wings; black w/ normal wings; black w/ vestigial wings.

• However, the observed phenotype was showed the two parental phenotypes, wild type and black w/ vestigial wings at a 1:1 ratio, and a smaller portion of recombinant offspring.

Fig. 15.6 Chromosomal basis for recombination of linked genes.

Linkage Mapping (Fig. 15.7)

• The frequency of recombination can be used to determine the distance between two loci, and the relative locations of genes on a chromosome.

• The distance between genes is expressed in map units.

– One map unit is equivalent to a 1% recombination frequency.

Fig. 15.8 A partial genetic map of a Drosophila chromosome

Cytological Mapping

• Cytological maps of chromosomes locate genes with respect to chromosomal feature, such as stained bands that can be seen in the microscope.

• http://www.accessexcellence.org/RC/VL/GG/fish.html

• The genetic basis of sex determination is not yet fully understood but one gene, SRY, on the Y chromosome plays a crucial role:

– This gene triggers testicular development

– In its absence ovaries develop rather than testes

• Other genes on the Y chromosome are also necessary for normal sperm production

Fig. 15.9 Some chromosomal systems of sex determination.

Sex Linked Genes

• Any gene on a sex chromosome is sex-linked

• Sex chromosomes contain both genes that determine sex and genes that are unrelated to sex determination

• The Y chromosome is 1/3 the size and carries 1/100 of the genes found on the X chromosome

• Most sex-linked genes unrelated to sex determination are found on the X chromosome

Figure 15.10 The transmission of sex-linked recessive traits

Sex Linked Genes – X versus Y

• Thus if a gene unrelated to sex determination is present on the X chromosome then it is unlikely to have a twin on the Y

• If this gene is recessive it will still be expressed in the male as there is no twin to counter it

• The female, having two X’s needs both to be recessive before the condition would be displayed

Sex Linked Disorders in Humans

• A number of human conditions result from sex-linked (X-linked) recessive alleles that are expressed more commonly in males than females

– Red-Green color blindness

• Involves several X-linked genes

• Normal color vision includes about 150 colors, but red-green color blindness involves fewer than 25

– Hemophilia – missing the blood clotting factor VIII.

– Duchene Muscular Dystrophy – the gene for dystrophin is mutated. Muscular wasting and severely shortened lifespan.

X-Inactivation in Female Mammals

• Females inherit two X chromosomes, however one X cell in each cell becomes inactivated.

• The inactive X condenses into a Barr body.

• Inactivation occurs randomly, early in embryonic development.

• Females consist of a mosaic of two types of cells.

Figure 15.11 X inactivation and the tortoiseshell cat

Calico cat

Errors in Chromosome Number

• Occasionally there are errors in meiosis called “non-disjunction”.

• The members of a pair of homologous chromosomes to not move apart properly in Meiosis I, OR

• The sister chromatids do not split in meiosis II.

• All the F₁ offspring had red eyes.

• The F₂ offspring had both red and white eyes, with a 3:1 ratio of red to white.

• All the F₂ females had red eyes, while half the F₂ males had red eyes and half had white eyes.

• The alleles are represented with the following symbols: b⁺ = gray body; b = black body; vg⁺=normal wings; vg = vestigial wings.

• Morgan mated true breeding wild-type flies (b⁺b⁺ vg⁺vg⁺) with true breeding black, vestigial-winged ones (bb vg vg).

• The F₁ generation were all wild type.

• He crossed the F₁ generation with true breeding black, vestigial-winged flies (bb vg vg).