The Chromosomal Basis of Inheritance

Chapter 15

REVIEW OF MENDEL’S DISCOVERIES:

The arrangement of chromosomes at metaphase 1 of meiosis and their movement during anaphase 1 account for the segregation and independent assortment of the alleles for seed color and shape.

Let’s look at figure 15.1 on text page 270 together!

REMEMBER:

Principle of Segregation: during the formation of gametes, the two traits (alleles) carried by each parent separate.

Principle of Assortment: States that each allele pairs of different genes segregates independently during gamete formation – applies when genes for two characteristics are located on different pairs of homologous chromosomes.

Beyond Mendel: Thomas Morgan Thomas Morgan was the first scientist to associate a

specific gene with a specific chromosome, early in the 20th century.

Morgan chose to work with fruit flies (Drosophila melanogaster), because: They are prolific breeders – a single mating will produce hundreds of

offspring A new generation can be bred every two weeks They have only four chromosomes – easily distinguishable with a

light microscope They have three pairs of autosomes and one pair of sex

chromosomes These characteristics make the fruit fly a convenient

organism for genetic studies!

Normal v/s Mutant Traits

The normal phenotype for a character (most common in natural populations) is referred to as WILD TYPE.

Traits that are alternatives to the wild type are called MUTANTS – because they are due to alleles assumed to have originated as changes in the wild-type allele.

Morgan – Tracing a Gene to a Specific Chromosome in Drosophila

Wild-type Drosophila flies have red eyes (bottom).

Morgan discovered a mutant male with white eyes (top).

This variation made it possible for Morgan to trace a gene for eye color to a specific chromosome.

Figure 15.3

Sex-Linked InheritanceWhen Morgan bred his mutant male to a wild-type female, all F1 offspring had red eyes. The F2 generation showed a typical Mendelian 3:1 ratio of traits, but the recessive trait – white eyes – was liked to sex.

All females had red eyes, but half the males had white eyes. Morgan hypothesized that the gene responsible was located on the X chromosome and that there was no corresponding locus on the Y chromosome.

Linked Genes

Number of genes in a cell is FAR greater than the number of chromosomes.

Linked Genes are genes that are located on the same chromosome and that tend to be inherited together .

Inheritance patterns with linked genes tend to deviate from expected Mendelian ratios: Morgan was the first to trace a gene to a specific

chromosome. Sex-linked genes are genes located on a sex

chromosome (X or Y chromosome).

Figure 15.9

EVIDENCE FOR LINKED GENES IN DROSOPHILA

This example explains that body color AND wing size must be linked – look at the expected v/s observed ratios in the offspring!

Pages 293

• Morgan determined that– Genes that are close together on the same

chromosome are linked and do not assort independently

– Unlinked genes are either on separate chromosomes of are far apart on the same chromosome and assort independently

Parentsin testcross

b+ vg+

b vg

b+ vg+

b vg

b vg

b vg

b vg

b vg

Mostoffspring

X

or

Genetic Recombination

Genetic Recombination is the general term for the production of offspring with new combinations of traits inherited from two parents

Organisms that have these are called “recombinants”

“parental types” would be offspring that phenotypically match either parent

In crossing over during prophase of meiosis I, chromatids of paired homologous chromosomes break, and homologous chromatid fragments switch places…crossing over. This creates recombinant chromosomes.

NOTICE the parental types and the recombinants created during Meiosis I in the diagram above.

Mapping Genetic Loci Genetics can use recombination data to map a chromosome’s

genetic loci! Method discovered by Alfred Sturtevant

Called a genetic map: an ordered list of the genetic loci along a particular chromosome. A linkage map is a genetic map based on recombination frequencies.

Assuming that cross-over possibility is approximately equal at all points on a chromosome, the further apart two genes are, the HIGHER the probability that a cross-over will occur between those two genes – the higher the recombination frequency REASONING: the greater the distance between two genes, the more

points there are between them where crossing over can occur. The distances between genes are called Map units, or

centimorgans in honor of Thomas Hunt Morgan. Equivalent to a 1% recombination frequency.

b = body color

cn = cinnabar eyes (brighter red)

vg = wing size

The probability of a crossover between two genetic loci is proportional to the distance separating the loci.

This simplified map shows just a few of the genes that have been mapped on Drosophila chromosomes II.

Notice that more than one gene can affect a given phenotypic characteristic, such as eye color.

Constructing a Linkage Map

• Determine the sequence of genes along a chromosome based on the following recombination frequencies: A-B = 8 map units A-C = 28 map units A-D = 25 map units B-C = 20 map units B-D = 33 map units

The Sex Chromosomes

In humans and other animals, there are two varieties of sex chromosomes: X and Y. XX = girl XY = boy

Anatomical signs of sex begin to emerge in humans when the embryo is about 2 months old. Before then, the rudiments of gonads are generic –

they can develop into either ovaries or testes, depending on hormonal conditions within the embryo.

Y chromosome must be present to produce testes.

Sex-Linked (x-linked) Genes Show up more often in the sex that has only one copy of

the X- chromosome! Fathers pass sex-linked alleles to all of their daughters but none

of their sons. Mothers can pass sex-linked alleles to both sons and daughters.

If a sex-linked trait is due to a recessive allele, a female will express the phenotype only if she is homozygous. BUT, a male receiving the recessive allele from his mother will ALWAYS express the trait – because his other allele is the Y chromosome!

Human examples of sex-linked disorders: Duchenne muscular dystrophy Hemophilia Baldness

Sex-linked genes follow specific patterns of inheritance

Figure 15.10a–c

XAXA XaY

Xa Y

XAXa XAY

XAYXAYa

XA

XA

Ova

Sperm

XAXa XAY

Ova XA

Xa

XAXA XAY

XaYXaYA

XA YSperm

XAXa XaY

Ova

Xa Y

XAXa XAY

XaYXaYa

XA

Xa

A father with the disorder will transmit the mutant allele to all daughters but to no sons. When the mother is a dominant homozygote, the daughters will have the normal phenotype but will be carriers of the mutation.

If a carrier mates with a male of normal phenotype, there is a 50% chance that each daughter will be a carrier like her mother, and a 50% chance that each son will have the disorder.

If a carrier mates with a male who has the disorder, there is a 50% chance that each child born to them will have the disorder, regardless of sex. Daughters who do not have the disorder will be carriers, where as males without the disorder will be completely free of the recessive allele.

(a)

(b)

(c)

Sperm

X-Inactivation in Female Mammals

Only one X chromosome stays active in females – the other becomes inactivated during embryonic development. The inactive X in each cell of a female condenses into a

compact object – a Barr Body Barr body chromosomes are reactivated in the

ovary cells that give rise to ova. See page 291-292 and discussion of tortoiseshell cat.

XIST is a gene that is active ONLY on the Barr-body chromosome.

Mary Lyon and the inheritance of inactivation: page 292

Mutations

Mutations are changes in DNA that also change the protein produced. Can happen spontaneously (no reason they

occurred).

-OR-

By mutagens – substances or agents that can cause changes in DNA

Ex. Chemicals, radiation, x-rays, viruses

“Unseen” Changes

Changes can occur without the organism showing an effect! NOTE: changes DO occur that are not true “mutations” –

protein production not affected

These occur in the INTRON areas of chromosomes, and as long as the length of the code is not affected, they will not be seen in the organism…

Mutations in Reproductive Cells

Changes in reproductive cells:code is changed in sperm or eggwon’t effect the parent, but CAN effect the

offspring produced from those altered sex cells

can be POSITIVE – new, adaptive traits

Mutations in Body Cells

Changes in body cells:Are not passed on to offspring, but can cause

MAJOR complications for the individual effected

Ex. Solar radiation – skin cancerAgain the process is thought to be cumulative

effect of exposure to mutagens over time.

Point Mutation v/s Chromosomal Mutation

Point Mutation: change in a single base pair of DNA.

Chromosome Mutation: change in a large portion of an entire chromosome – effects MANY genes.

Point Mutations

Point mutation: change in single base pair of DNA

if the mutation does not effect the length of the code, it will just change the amino acid in that position

Ex: SUBSTITUTION

If the mutation does change the length of the code, is called a frameshift mutation, and are two types:

Ex: INSERTIONS AND DELETIONS

Gene Mutations – Effect Only ONE Base in the Code

Examples: Substitutions, Insertions, Deletions

Gene Mutations only affect ONE point of the code -- often called Point Mutations

Chromosomal Mutations

Can effect chromosome number AND chromosome shape:Mistakes in numbers of chromosomes

such as nondisjunction (where members of a pair of homologous chromosomes do not move apart properly resulting in offspring that have):

Aneuploidy – abnormal chromosome number – can be (Trisomy or Monosomy or Polyploidy)

Either type of meiotic error will produce gametes with an abnormal chromosome number.

Trisomy 21 – Down Syndrome

Karyotype showing trisomy 21 – individual has three #21 chromosomes. Child will exhibit facial characteristics of Down syndrome.

Trisomy 16 – Major Cause of Miscarriage in 1st Trimester Pregnancy

Monosomy X – Turner Syndrome

XO individuals are phenotypically female, but their sex organs do not mature at adolescence, and they are sterile. Most have normal intelligence.

XXY – Klinefelter Syndrome

XXY – Klinefelter Syndrome – have male sex organs, but testes are abnormally small and the man is sterile. Often includes breast enlargement and other feminine body characteristics.

Males XYY – not characterized by a particular syndrome, but usually are somewhat taller than average.

Fragile X Syndrome

Named for the physical appearance of an abnormal X chromosome, the tip of which hangs on to the rest of the chromosome by a thin thread of DNA.Mental retardation – more common in males

and usually inherited by Mother.

Autosomal Dominant Genes – body cells, not passed on to offspring

Autosomal Recessive Genes – body cells, not passed on to offspring

X-linked recessive Genes – sex cells, passed on to offspring Y-linked – only in males Chromosomal Abnormalities – if affects sex chromosomes,

passed on to offspring Multifactorial – genetic component (gene or chromosome)

plus a significant environmental influence

Mitochondrial DNA comes from Mom – maternal inheritance, because mitochondria passed on by zygote all come from the cytoplasm of the ovum