Chromosomes, Genes & Alleles

What Are Chromosomes?

Chargaff’s Ratios Every species contains identical quantities of complimentary

base pairs But different species can have differing ratios of GC to TA DNAi ANIMATION

Packaging DNA is made up of 2 parallel strands of complimentary

nucleotides attached to a deoxyribose-phosphate backbone Negatively charged DNA is wrapped around positively charged

histone proteins to form a nucleosome Histones in adjacent nucleosomes interact to form chromatin Strands of chromatin are folded around a protein scaffold to

form chromosomes (this only occurs during cell division) DNAi ANIMATIONS x 2

Prokaryotes vs Eukaryotes

DNA is packaged in to structures called chromosomes

Eukaryotic chromosomes are linear strands 1 set = haploid 2 sets = diploid >2 sets = polyploid

Prokaryotic chromosomes are circular Prokaryotic DNA considered to be “naked” as there is

very little packaging

Chromosomes in Humans

A Karyotype is the full complement of chromosomes in a particular species.

Humans have 22 pairs of homologous (matched) autosomes

We also have one pair of non-homologous (unmatched) sex chromosomes

Human Karyotype

Chromosomes differ with regard to their size, banding pattern and location of centromere.

The position of a particular gene on one of these chromosomes is referred to as its locus (plural: loci)

Other species

Chromosome number is not an indication of the complexity of a species.

Sex Chromosomes

The X chromosome may carry up to 1500 genes, the Y, only 300 and may be degenerating

In humans the default sex is female

Sex is determined by the male, via expression of the SRY gene located on the Y chromosome

Kleinfelter’s Syndrome

Due to a mistake in meiosis, an individual inherits an extra X chromosome (47 XXY) Occurs in 1/650 males but is asymptomatic in 500 of

these Extremely variable symptoms Small testes and reduced fertility Lanky build / youthful features Reading / language impairment Motor impairment Rounded body type Gynecomastia (increased breast tissue)

Turner’s Syndrome

Due to a mistake in meiosis, an individual inherits an only one sex chromosome (45 X) Occurs in 1 in 2000-5000 Phenotypically female Short stature, broad chest Low hairline, low-set ears Webbed neck Undeveloped ovaries Diabetes, heart disease Vision problems Learning difficulties

Sex chromosomes in other species

All mammals operate using the XX/XY systemThe system in birds and some reptiles is WZ/ZZ

Males have a homologous ZZ genotype Females determine the sex of offspring due to being WZ

In reptiles such as green sea turtles and crocodiles, sex is determined by incubation temperature. Turtles:>31◦ = male, <28◦ = female, 29-30◦ = male/female

The karyotype of an individual can be represented symbolically

Human female = 46 XXFemale tiger snake = 34 WZ

Genes

The number of genes varies between species, and as can be seen is not indicative of species complexity

Other than humans, the above species are very useful for genetic studies, WHY?

Answer = very short generational life cycles

Common name

Species name No. of genes

Human H. sapiens 25,000

Mustard plant A. thaliana 27,000

Nematode worm

C. elegans 20,000

Fruit Fly D. melanogaster

14,000

Baker’s yeast S. cereviciae 6,000

Gut bacterium E. coli 4,000

Genome

The genome of a species is not just the number of genes, but the entire genetic complement

Amoeba are rumored to be genetic hoarders, their junk (non-coding) DNA is retained to provide them with greater adaptability to a changing environment

Organism Genome size (in millions of base pairs

Fruit fly 180

Snake 3,100

Human 9,300

Fern 160,000

Amoeba 670,000

Genes, genome, genotype

Only a small percentage of our DNA actually codes for a particular function

The remainder, non-coding DNA, is slowly being discovered not to be all junk (more on this later)

The position of a gene on a chromosome can be mapped:

The position of a gene on a chromosome is identical in both maternal and paternal copies

LDLR gene

Naming Genes

Genes are usually named after the functions that they control.

Alleles

Functions can be controlled by one or many genesThese genes can exist in different forms, called allelesAlleles will code for a specific phenotype (outward

expression of genotype)Alleles are usually represented by letters of the alphabetCapital letters are used to express whether the allele is

dominant or recessiveeg. Genetic instructions for making a chocolate cake could

be: Allele 1 = put cherries on top (C) Allele 2 = put strawberries on top (c)

There can be many more than 2 alleles for a particular gene, but an individual can only possess 2 of these.

Genotype

Your genotype is a way of expressing the two alleles that you hold for a particular gene

Human eye colour is controlled by one gene in particular, for which there are only 2 available alleles B – codes for phenotypically blue eyes (dominant) b – codes for phenotypically brown eyes (recessive)

You need only 1 copy of a dominant allele for it to be expressed

You need 2 copies of a recessive allele for it to be expressed BB = bb = Bb =

Brown eyes

blue eyes

Brown eyes

Genotype - vocabulary

When one possesses identical alleles on the maternal and paternal chromosome, this is referred to as a homozygous genotype. eg BB = homozygous dominant eg bb = homozygous recessive

Having two different alleles is a heterozygous genotype.

If you only have one copy of the chromosome in question (eg X or Y in males) and therefore only one copy of the gene, this is a hemizygous genotype eg SRY gene / male pattern baldness

Some alleles can be co-dominant or display incomplete dominance

Carriers

An individual with an unexpressed recessive allele is said to be a carrier for a trait.

Even though they do not express this trait, if they have offspring with another individual who is also recessive for the trait, they may produces homozygous recessive offspring.

eg. Albanism is a recessive trait, two parents who are carriers for the trait (Aa x Aa) can have an albino child (aa)

Multiple alleles & dominance

There can be many more than 2 alleles for a particular gene, but an individual can only possess 2 of these.

A good example is the ABO blood type system in humans. If blood type is represented as the letter i, capitalisation will represent dominance and lower case represents recessiveness. IA = type A blood IB = type B blood i = type O blood

The following represents all combinations and results: Blood type A = genotypes IAIA & IAi Blood type B = genotypes IBIB & IBi Blood type AB = genotype IAIB

Blood type O = genotype ii

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Phenotype

The expression of a gene is determined by the combination of dominant and recessive alleles possessed by the individual

The ABO blood group system represents not only a gene with multiple alleles, but also a system of codominance (IA & IB are codominant and i is recessive)

Phenotypic expression is not always visible, it can be physical, biochemical or physiological

Incomplete dominance

Incomplete dominance is when two alleles are neither dominant nor recessive to each other

The result is a phenotype that is a blend of the parents.

Red flowers (RR) and white flowers (WW) will produce pink flowers (RW)RR RW WW

Co-dominance

Co-dominance is when two equally dominant alleles are both expressed in the phenotype.

eg. Some cattle can have red hair (RR) or white hair (WW), if these are crossed, the produce roan (RW) offspring.

Roan is not a blend, these cattle have both completely red and completely white hairs

One or many genes

Not all traits are controlled by a single gene, many are controlled by multiple genes.

ABO Blood groups are controlled by a single gene and show discontinuous variation

Height is controlled by multiple genes and shows continuous variation

B O ABA Height in cm

Sex-linked traits

Traits governed by genes that are located on a sex chromosome are said to be sex-linked, or more specifically x-linked or y-linked.

An example is male pattern baldness (x-linked, recessive)

This trait is quite uncommon in females as two copies of the allele are required (XbXb)

With only one copy, they are an asymptomatic carrier (XbX)

As males are hemizygous for genes on the X chromosome, a single copy results in expression of the trait (XbY)

Relationship between genotype & phenotype

Blue and pink hydrangeas are genetically identical.

In acidic soils (low pH) the flowers are blueIn alkaline soils (high pH) the flowers are

pink

PKU & Phenotype

Phenylketonuria is a serious genetic disorder in humans resulting in very low production of the enzyme phe hydroxylase.

Phenylketonurics cannot metabolise large quantities of the amino acid phenylalanine (phe).

In their developmental years, if fed food containing large amounts of phe, this will result in mental impairment.

If put on a low phe diet, development will be normalSo same genotype, different phenotype

Genotype: pp, Phenotype: PKU with mental impairment Genotype: pp, Phenotype: PKU with normal development

Siamese cats and temperature

Siamese cats and temperature

Precursor → pigment

Tyrosinase will only catalyse this reaction when temperature is lower than body temperature

These cats are born whitePigmentation occurs in

extremities due to lower temperature

tyrosinase

Phenotypic Complexity

Female cats and other species will sometimes display evidence of X-inactivation

This is where phenotype is determined by the allele on one X in some cells and the other X in other cells.

The tortoiseshell colouring is a product of the different expression within the follicle-producing cells in a XoX+ cat (Xo = orange, X+ = black).

Male tortoiseshell cats (rare) will usually be XXY.

A new layer to phenotypic complexity

The internal structure and organisation of DNA can also effect phenotypic expression.

Eg. methyl groups or chromatin remodellingAn identical mutation can have very different

effects dependent on whether is on the maternal or paternal copy of the chromosome.

Eg. Mutation on chromosome 15 at the q11.2-13 locus

Praeder-Willi Syndrome

If mutation occurs on the paternal chromosome …

The result is Praeder-Willi Syndrome Learning difficulties Insatiable hunger Behavioural problems

Angelman Syndrome

If mutation occurs on the maternal chromosome …

The result is Angelman Syndrome Severe learning difficulties Jerky movements Behavioural problems