Chapter 15: The Chromosomal

Basis of Inheritance

The Chromosomal Theory of Inheritance• Genes have specific loci on

chromosomes and chromosomes undergo segregation and independent assortment

Chromosomal Linkage

Thomas Morgan (early 20th century)Drosophilia melanogaster(fruit flies)Associated a specific gene with a specific chromosome

Morgan’s Experiment

P1: Mated white eyed male with red eyed female

F1: 100% red eyedF1 generation mated

F2: 3 red : 1 whiteHowever???

Morgan’s Experiment:

All females were red eyes:Half the males were red

The other half were white

Morgan’s Conclusion:

1.1. Eye color was linked to sex2.2. specific genes are carried on

specific chromosomes3.3. genes located on sex

chromosomes exhibit unique inheritance patterns

Linked Genes:

Sex-linkage: genes located on a sex chromosome

Linked genes: genes located on the same chromosome that tend

to be inherited together

Another Morgan Experiment:

This time he observed body color and wing size:

Wild type = gray body (b+) and normal wings (vg+)

Mutant type = black body (b) and vestigial wings (vg)

First Cross: true breeding wild type wit black vestigial

wingsb+b+vg+vg+ X bbvgvg

F1 = all wild type phenotype(b+bvg+vg)

Second Cross: female dihybrids vs

true breeding reeessive males

b+ bvg+vg X bbvgvg(test cross)

2300 offspring were scored

Results:-High proportion of parental phenotypes(965 wild type, 944 black vestigial)

-Low proportions of non- parental phenotypes

(206 gray vestigial, 185 black normal)

Conclusion: 1. Body color and wing size are

usually inherited together(genes must be on the same

chromosome??)

Conclusion: 2. Body color and wing size are

only partially linked:

Explaining Morgan’s Results:Recombination of unlinked genes vs.

linked genes: Unlinked genes = independent

assortmentLinked genes = crossing over

Recombination:Production of offspring with

combinations of traits different from those found in

either parent!

Genetic Mapping:

Genetic maps are an ordered list of the genetic loci along a

particular chromosome

Genetic mapping:

Recombination frequencies depend on distances between genes on a

chromosome

Recombination frequency refers to the percentage of

recombinants occurring in the

offspring

Alfred Sturtevant: hypothesis

*crossing over is a random event*the farther apart the genes on a

chromosome, the higher the probability that crossing over will

occur, so the higher the recombination frequency

Sturtevant Reasoning:

The further apart two genes are, the more points between them where crossing over can occur.

Linkage Map:

Probability of crossover between two genetic loci is proportional to the distance separating the two

loci. *experimental crosses reveal recombination frequencies

Example: Drosophila

Body color (b)Wing size (vg)Cinnabar (cn)

Map units: Distance between genes on a

chromosome1 map unit = 1% recombination

frequency

Seed and flower color in pea

plants:Genes that are very far apart on

the chromosomeCrossing over is almost certain.

Frequency of crossing over is not

uniform over the length of the chromosome

Map units do portray order of genes on a chromosome

Human sex-linkage

• The X-Y system: • Sex of offspring is determined by the

sperm.• Fathers pass Y chromosome to sons• Fathers pass X chromosome to daughters

• Mothers donate the X chromosome to sons and daughters

Human sex-linkage

• SRY gene: gene on Y chromosome that triggers the development of testes• Sex determining region of

the Y chromosome• If Y chromosome is present,

gonads (first two months are generic) will develop into testes.

Sex lined genes:

• Genes that are located on the sex chromosome• Genes that may code for

characteristics unrelated to sex• Recessive sex linked traits:

• Females must be homozygous• Males are hemizygous

Sex-Linked Disorders:

•Color-blindness• female- must have a color

blind father and carrier mother.

Sex-Linked Disorders:

•Duchenne muscular dystropy (MD); hemophilia• Defective dystrophin

protein

Sex-Linked Disorders:

•X-inactivation: 2nd X chromosome in females condenses into a Barr body (e.g., tortoiseshell gene in cats)• Except in ovaries where it

becomes reactivated

Sex-Linked Disorders:

•Hemophilia: absence of one or more of the proteins responsible for blood coagulation• Queen Victoria pedigree

Chromosomal Errors:

• Nondisjunction: members of a pair of homologous chromosomes do not separate properly during meiosis I or sister chromatids fail to separate during meiosis II

Chromosomal Errors:

• Aneuploidy: chromosome number is abnormal• Monosomy: missing chromosome

• Turner Symdrome -XO • Trisomy : extra chromosome

• Down syndrome- Trisomy- 21• Kleinfelters Syndrome- XXY

• Polyploidy: extra sets of chromosomes

Chromosomal Errors:

• Alterations of chromosomal structure:

• Deletion: removal of a chromosomal segment

• Duplication: repeats a chromosomal segment

• Inversion: segment reversal in a chromosome

• Translocation: movement of a chromosomal segment to another

Point mutations: affect protein structure and

function• Base pair substitution: one

nucleotide pair replacing another

• Missense vs. Nonsense mutations• Missense = altered codon still codes for an

amino acid – not necessarily the right one• Nonsense = changes the codon to a stop

codon• Premature termination leading to malfunctional

proteins.

Insertions and Deletions:

• Adding or losing a nucleotide pair

• Disastrous effect on the protein

• Causes a Frame Shift:• Nucleotides down stream of the

mutation will be improperly grouped into codons that will likely produce a non- functional protein

Genomic imprinting

• a parental effect on gene expression

• Identical alleles may have different effects on offspring, depending on whether they arrive in the zygote via the ovum or via the sperm.

• Fragile X syndrome: higher prevalence of disorder and retardation in males

Inheritance of Organelles:

• Some genes are considered extranuclear:• That is not found in nucleus• But, in organelles such as mitochondria

and chloroplasts

• These genes do not follow mendelian inheritance patterns• Randomly assorted to gametes and

daughter cells

Inheritance of Organelles:

• Organelles are inherited maternally• Sperm only contributes

genetic information

Mutations:

• Plant variegation: due to mutations in the genes that control plant pigments• Pattern of variegation is determined by

the ratio of wild type allele vs. mutant type allele for pigmentation

Mitochondria DNA mutations:

• Heteroplasmy: when a cell contains both wild type and mutant type mtDNA.• Disorders usually affect nervous

and muscular systems• They require the most energy from

ATP

Mitochondria DNA mutations:

• Disorders of the optic nerve (leber’s neuropathy) and other eye defects.

• Kearns- Sayre Syndrome- abnormal heart rate and central nervous system disorder

• Mitochondrial myopathy: muscle deterioration, intolerance to exercise