+

Chromosome Basis of Inheritance

GENETIC INFORMATION

Gene – basic unit of genetic information. Genes determine the inherited characters.

Genome – the collection of genetic information.

Chromosomes – storage units of genes.

DNA - is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life

HUMAN GENOME

Most human cells contain 46 chromosomes

2 sex chromosomes (X,Y):XY – in males.XX – in females.

22 pairs of chromosomes named autosomes.

+Chromosome Theory of Inheritance

Genes have specific locations (loci) on chromosomes.

It is the chromosome that segregates and assorts independently.

How does this relate to Mendel’s laws of inheritance?

+What is the difference between an Autosome and a Sex-chromosome?

Autosomes are the first 22 homologous pairs of human chromosomes that do not influence the sex of an individual.

Sex Chromosomes are the 23rd pair of chromosomes that determine the sex of an individual.

+ Autosomal Traits Genes located on Autosomes control Autosomal traits and

disorders.

2 Types of Traits: Autosomal Dominant Autosomal Recessive

+Sex Linked Genes in Humans

Characteristics that are inherited from genes found on the sex chromosomes

Normally on the X chromosome as the Y chromosome is small and has very few genes.

Most seX-linked traits are recessive

More common in males than females Males only needs to inherit

one sex-linked recessive allele from mom to be expressed

Females has to inherit two sex-linked recessive alleles for expression

Examples Red-green color

blindness

Hemophilia

+ Sex Linked Traits

It is possible for a female to be a carrier of an X-linked trait, but not express it

SRY gene: gene on Y chromosome that triggers the development of testes

Fathers= pass X-linked alleles to all daughters only (but not to sons

Mothers= pass X-linked alleles to both sons & daughters

Men will express all X-linked traits they inherit

X-linked recessive, carrier mother

Unaffectedson

Unaffecteddaughter

Affectedson

Carrierdaughter

Unaffectedfather

Carriermother

Carrier

Affected

Unaffected

+Discovery of Sex-Linked Genes

Thomas Hunt Morgan in The Fly Room! (Columbia University 1910)

Fruit Flies (Drosophila melanogaster)

http://nobelprize.org/nobel_prizes/medicine/articles/lewis/index.html

© 2007 Paul Billiet ODWS

+Chromosomal Linkage

Thomas Hunt Morgan Drosophilia melanogaster

XX (female) vs. XY (male) Sex-linkage: genes located

on a sex chromosome Linked genes: genes located

on the same chromosome that tend to be inherited together

+Sex-Linked Recessive Pedigree Draw a Pedigree showing a cross between a

Red eyed Male fruit fly and a Carrier Female fruit fly which have 2 males and 2 females. (Show all possibilities) Red is dominant to white.

Genotypes of Parents:

Male = XR Y Female = XR Xr

XRY XRXr

XRY XrY XRXR XRXr

+Rules for Sex-Linked Recessive TraitsMore males than females are affected.An affected son can have parents who have

the normal phenotype. (XAY x XAXa)For a daughter to have the trait, her father

must also have it. Her mother must have it or be a carrier. (XaY, XaXa, XAXa)

The trait often skips a generation from the grandfather to the grandson.

If a woman has the trait (XaXa), all of her sons will be affected.

Pedigrees show only female carriers but no male carriers.

+ Examples of Sex-Linked Recessive Disorders

Red/Green Colorblindness – Difficulty perceiving differences between colors (red or green, blue or yellow).

Hemophilia – Absence of one or more proteins necessary for normal blood clotting.

Deafness

Cataracts – opacity in the lens that can lead to blindness

Night blindness – (Nyctalopia) rods do not work so that can not see in the dark

Glaucoma – pressure in the eye that can lead to optic nerve damage and blindness

Duchenne Muscular Dystrophy – progressive weakness and degeneration of skeletal muscles that control movement due to absence of dystrophin (protein that maintains muscle integrity). Mainly in boys, onset 3-5 yrs, by 12 years can’t walk, and later needs respirator.

+X- Inactivation

X-inactivation is a process by which one of the two copies of the X chromosome present in female mammals is inactivated (methylation)

X-inactivation occurs so that the female with two X chromosomes does not have twice as many X chromosome gene products as the male, which only has a single copy of the X chromosome

Inactivation is random

The coloration of tortoiseshell cats is a visible manifestation of X inactivation. The black and orange alleles of fur color are on the X chromosome. For any given patch of fur the inactivation of an X chromosome that carries one gene results in the fur color of the other active gene.

+X- Inactivation

Barr Bodies The inactive chromosome

condenses into a Barr body, which lies along the inside of the nuclear envelope

In men and women with more than one X chromosome, the number of Barr bodies visible at interphase is always one less than the total number of X chromosomes. For example, men with a 47,XXY karyotype have a single Barr body, whereas women with a 47, XXX karyotype have two Barr bodies

GENE LINKAGE

Genes are located on the same chromosomeAlleles cannot separate according to the laws of

Independent Assortment and Random Segregation

Unless…crossing over during meiosis I moves them to a different chromosome.We measure the distance between genes by the

frequency of crossing over moving one of them to a new chromosome, called gene linkage mapping

Distant genes are separated by crossing over more often than nearby genes.

Genetic RecombinationResults in offspring with a new combination of genes inherited

from the parents Parental Type

Some offspring will have same phenotype as one of the parentslaws of Independent Assortment and Random Segregation

RecombinantsSome offspring will have phenotypes different from both

parents

GENE LINKAGE

C is farther away from A than B is

We figure this out because a higher percentage of gametes are ABc than are Abc.

In fruit flies, wings and body color are linked

+ Linkage Map

Genetic map that is based on the percentage of cross-over events

A map unit is equal to a 1% recombination frequency.

Map units are used to express relative distances along the chromosome.

+Genetic recombination Summary

Crossing over Genes that DO NOT assort

independently of each other

Genetic map The further apart 2 genes

are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency

Linkage maps Genetic map based on

recombination frequencies

+Chromosomal Mutations

Damage to chromosomes due to physical or chemical disturbances or errors during meiosis.

Two Types of Chromosome Mutations:

1. Chromosome Structure

2. Chromosome Number

+ Problems with Chromosome Structure:

Deletion – during cell division, especially meiosis, a piece of the chromosome breaks off, may be an end piece or a middle piece (when two breaks in a chromosome occur).

Inversion – a segment of the chromosome is turned 180°, same gene but opposite position

Translocation – movement of a chromosome segment from one chromosome to a non-homologous chromosome

Duplication – a doubling of a chromosome segment because of attaching a broken piece form a homologous chromosome, or by unequal crossing over.

+ Structural Errors

+ Problems with Chromosome Number

Nondisjunction When members of a pair of homologous

chromosomes do not separate properly during meiosis I

Sister chromatids don’t separate properly during meiosis II

+ Chromosomal Mutations

Monosomy and Trisomy due to Nondisjunction members of homologous

chromosomes do not move apart in Meiosis I or sister chromatids do not separate during Meiosis II leaves one cell with too few chromosomes and one cell with too many.

Triploids develop from the fertilization of an abnormal diploid egg, produced from the nondisjunction of all chromosomes.

Tetraploids develop from the failure of a 2n zygote to divide after replicating its chromosomes, subsequent mitosis would produce 4n embryo.

+ Chromosomal Mutations

Polyploidy is common in the plant kingdom, spontaneous origin of polyploid individuals plays important role in evolution of plants.

In the animal kingdom, natural occurrence of polyploids is extremely rare.

In general, polyploids are more nearly normal in appearance than having monosomy or trisomy, which is more disruptive to have one extra chromosome in a pair.

Summary Nondisjunction:

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

Aneuploidy: chromosome number is abnormal• Monosomy~ missing chromosome• Trisomy ~ extra

chromosome (Down syndrome)• Polyploidy~ extra sets

of chromosomes

+Genomic imprinting

Genonmic imprinting is 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

+Trisomy 21

Trisomy 21 is the presence of 3 chromosome 21’s.Condition is called Down SyndromeCharacteristics are specific and familiar but not all individuals show the exact same characteristics.

+Down Syndrome

Individuals with Down syndrome have a typical facial appearanceAll have some degree of mental retardation, but for most it is mild to moderate.

Can learn to read, write, do some math, and live day-to-day with minimal assistance.

Others require a lot of attention and care

+Down Syndrome

There are several possible health concerns, including heart problems and hearing loss.

Individuals are now living longer than in the past, into their 50’s and 60’s

We are now discovering that those individuals who survive to this age are at very high risk for developing Alzheimer’s disease

+Klinefelter SyndromePeople with this disorder develop as males with subtle characteristics that become apparent during puberty.

Often tall and usually don't develop secondary sex characteristics, such as facial hair or underarm and pubic hair.

Different distribution of body fat, more than usual in the chest and hips.

May have some degree of mental retardation.

Some individuals are never diagnosed.

+Klinefelter Syndrome

Affects about 1 in 1000 malesThe extra X chromosome primarily affects the testes, the most common feature being infertility

2% of infertile men are diagnosed with Klinefelter syndrome

+Turner Syndrome

Affects about 1 in 5000 newborn girls.Estrogen and other growth hormones are not produced in sufficient quantity.When caught in infancy, TS can be managed and treated with regular medical care.

+Turner Syndrome

Females with Turner are shorter than average and can have other noticeable physical features.

Broad chest, swelling in hands and feet, webbed neck.

Other health issues can include heart disease, horseshoe shaped kidneys, learning disabilities