The

Chromosomal

Basis of

Inheritance

Factors and Genes

Mendel’s model of inheritance was based on the

idea of “factors” that were independently assorted

and segregated into gametes

We now know that these factors are actually genes

that are located on chromosomes

Concept 15.1 Mendelian inheritance has its

physical basis in the behaviour of

chromosomes

• Mendel’s laws of segregation and independent assortment can be accounted for by the

behaviour of chromosomes during meiosis

• Morgan’s experiments with Drosophila provided

the first evidence that specific genes are

associated with specific chromosomes

Genes and Chromosomes Even after chromosomes were visualized and

observed through microscopy, there were no

indications that Mendel’s factors were related to

the chromosomes

It was only in the early 1900s when scientists noticed

similarities between meiosis and Mendel’s model

Chromosome Theory of Inheritance Genes have specific loci (positions) along

chromosomes

Chromosomes undergo segregation and

independent assortment

Thomas Hunt Morgan

Morgan conducted experiments with Drosophila

melanogaster (fruits flies)

Drosophila have many offspring and only 4 pairs of

chromosomes

He mated many pairs of Drosophila until a mutant

trait (different from the common wild type) was

found in a male fly that had white eyes as opposed

to the common red eyes.

This fly was then mated to red eyed females

P generation

female (wild-type eyes) X

male (mutant eyes)

F1 generation

All offspring display wild-type

phenotype

F2 generation

Offspring exhibit a 3:1 ratio of

wild-type to mutant eyes

Results similar to Mendel`s

data with pea plants.

However, only males

displayed the white eyed

phenotype.

Possibility of correlation with

sex chromosome.

Concept 15.2 Sex-linked genes exhibit unique

patterns of inheritance

• Sex chromosomes determine sex

• Sex-linked genes on sex chromosomes have a

unique pattern of inheritance

The Chromosomal Basis of Sex

The X-Y System

Human sex chromosomes are known as the X-

chromosome and Y-chromosome

The Y-chromosome is the smaller chromosome, with

the shorter arms containing regions that are

homologous to regions of the X-chromosome.

XX develops as a female, XY develops as a male

Therefore, the male gamete determines the sex of

the offspring with a fifty-fifty chance (X to for a

female and Y for a male)

Inheritance of Sex-Linked Genes

A sex-linked gene is a gene on a sex chromosome

Although a gene appears on a sex chromosome, it is not necessarily related to sex determination or sex characteristics

If a recessive sex-linked trait is on the X-chromosome, a female must be homozygous recessive for the trait to display the phenotype.

Alternatively, a male only has one copy of the X-chromosome. Therefore there is no possibility to be heterozygous for that gene.

Examples: colour blindness, hemophilia

X Inactivation in Female Mammals

While females have two X-chromosomes, they do

not make double of the proteins coded for by the

X-chromosomes

In each cell, one of the X-chromosomes will

become inactivated through DNA methylation

This inactive X-chromosome condenses into a Barr

body that remains near the nuclear envelope

The X-chromosome that is inactivated in each cell is

random, meaning that each female has a mosaic

of two cell types

Concept 15.3Linked genes tend to be inherited

together because they are located

near each other on the same

chromosome

• Mendel’s law of independent assortment dictates that genes segregate independently of each other. However, genes that are closer together do not always sort independently and are considered linked

• Recombination frequencies between genes can be used to map genes on a chromosome

Chromosomes and Linked Genes

Each chromosome has hundreds or thousands of

genes

Linked genes are genes located on the same

chromosome that tend to be inherited together

These linked genes cause deviations from the

expected outcome of Mendel’s law of

independent assortment.

How Linkage Affects Inheritance In Mendel’s experiments, he observed that some

offspring have combinations of traits that do not

match either parent in the P generation

We now know this is due to crossing over of

chromosomes during meiosis

Gametes from green-wrinkled homozygousrecessive parent (yyrr)

Gametes from yellow-roundheterozygous parent (YyRr)

Parental-type offspring

Recombinantoffspring

YyRr yyrr Yyrr yyRr

YR yr Yr yR

yr

How Linkage Affects Inheritance

In Morgan’s experiments, inheritance of certain

traits were found to deviate from Mendel’s law of

independent assortment.

For the characteristics of body colour and wing

type, there are two observable phenotype.

The wild-type phenotypes are grey bodies and

normal-sized wings. The mutant phenotypes are

black bodies and small vestigial wings.

Morgan found a higher proportion of parental

phenotypes than would be expected from

independent assortment

Cross between two flies that are true-breeding for

two different genes that follow a two-allele

complete dominance mode of inheritance.

Recombination

The offspring that show new combinations of the

parental traits are known as recombinant offspring

If 50% of all offspring are recombinants, then there is

a 50% frequency of recombination.

Based on his results, Morgan proposed that some

process must occasionally break the physical

connection between genes on the same

chromosome

This process is the mechanism of crossing over which

occurs between homologous chromosomes

Linked Genes

The further apart genes are, the more likely they are

to assort independently and recombine in new

combinations during crossover.

If the frequency of recombinants is less than 50%,

the genes are likely linked (closer together on the

same chromosome).

Mapping the Distance Between

Genes Using Recombination Data

After the discovery of linked genes and recombination due to crossing over, one of Morgan’s students came up with a method for constructing a genetic map.

Genetic map - An ordered list of the genetic loci along a particular chromosome.

Linkage map – A genetic map based on recombination frequencies

His prediction: The farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency

Concept 15.4 Alterations of chromosome number

or structure cause some genetic

disorders

• Nondisjunction during meiosis can result in abnormal chromosome number

• Chromosomal breakage can result in abnormal

chromosome structure

• Chromosomal abnormalities can lead to various disorders

Abnormal Chromosome Number

Nondisjunction – Error in segregation of homologous

chromosomes or sister chromatids during meiosis

Abnormal Chromosome Number

Aneuploidy – Zygote produced with an abnormal

number of chromosomes

Monosomic – missing chromosome in an aneuploid

zygote

Trisomic – extra chromosome in an aneuploidy

zygote

Polyploidy – extra chromosome set in an aneuploid

zygote

Alterations of Chromosome

Structure

Deletion – removes a chromosomal segment

Duplication – repeats a chromosomal segment

Inversion – reverses a chromosomal segment

Alterations of Chromosome

Structure

Translocation – moves a chromosomal segment

from one chromosome to a nonhomologous

chromosome

Reciprocal translocation

– segments are exchanged Nonreciprocal translocation

– one direction, no exchange

Human Disorders Due to

Chromosomal Alterations

Down Syndrome (Trisomy 21)

Resulting from an extra copy of chromosome 21

(usually fro nondisjunction during meiosis I)

Frequency increases with age of the mother

Symptoms include characteristic facial features and

stature, heart defects and mental delay

Prone to other diseases

Human Disorders Due to

Chromosomal Alterations

Aneuploidy of Sex Chromosomes

Nondisjunction of sex chromosomes causing either an extra sex chromosome or a missing sex chromosome

Klinefelter syndrome (genotype XXY)

Male sex organs (though sterile) but may show female secondary sex characteristics

Males with an extra Y (XYY)

No real distinguishing features

Females with trisomy X (genotype XXX)

No real distinguishing features

Turner syndrome (genotype X0)

Phenotypically female but sterile. Need hormone therapy to development secondary sex characteristics

Human Disorders Due to

Chromosomal Alterations

Disorders caused by structurally altered

chromosomes (deletions, translocations, etc.)

Cri du chat

Results from a specific deletion in chromosome 5

Symptoms include mental retardation, unusual facial

features, a cat-like cry

Early death

Chronic myelogenous leukemia

Reciprocal translocation (between chromosome 22 and

9) during mitosis of cells that are precursors to white blood

cells

Concept 15.5 Some inheritance patterns are

exceptions to the standard

chromosome theory

• Genomic imprinting can inhibit certain alleles during gamete production, which then leads to relationships between allele expression and parental lineage (maternal or paternal)

• Extranuclear genes are usually passed on maternally through the cytoplasm and its contents

Genomic Imprinting Occurs during the formation of gametes and results

in the silencing of one allele of certain genes

Occurs differently in males and females so that

either the alleles are imprinted in the egg, or in the

sperm

Therefore, only one allele is expressed for each

imprinted gene, either male or female

Genomic Imprinting Imprinted alleles usually have alterations such as a

methylation of cytosine nucleotides

However, methylation can also result in activation

of expression of an allele

Affects only a small number

of genes

Not the same as sex-linked

alleles

Inheritance of Organelle Genes

Extranuclear genes exist outside the nucleus

They can be found in organelles such as

mitochondria or chloroplasts

Theses organelles are obtained from the egg and

therefore the offspring will inherit

these specific extranuclear genes

from the maternal source

Extranuclear gene disorders

Mitochondrial myopathy

Weakness, intolerance of exercise, muscle

deterioration

Leber’s hereditary optic neuropathy

Sudden blindness in 20s or 30s

Possible connection to may other disorders