Inheritance

Gene

A sequence of DNA that codes for a polypeptide and which occupies a specific locus of a chromosome

Alleles

a version of a gene

Locus

Homozygous

Heterozygous

Genotype

Phenotype

• Locus – the position of the gene on the chromosome.

• Homozygous – both alleles for a gene are the same.

• Heterozygous – the two alleles for a gene are different.

• Genotype – the alleles an individual contains.

• Phenotype – a description of the characteristic in words.

Dominant and recessive

• Dominant – an allele which always expresses itself.

• Recessive – an allele which will not express itself in the presence of a dominant allele.

Monohybrid and Dihybrid

• Monohybrid inheritance – the inheritance of one pair of contrasting characteristics.

• Dihybrid inheritance – the inheritance of two pairs of contrasting characteristics.

F1 and F2

• F₁ – First filial generation – first generation produced in a cross.

• F₂ – Second filial generation – second generation produced in a cross.

Mono hybrid Inheritance

The inheritance of a single gene for a characteristic eg. Height

Mendels conclusion

• Characteristics do not blend.

• Characteristics are controlled by particles or factors. We call these genes.

• These factors are passed from generation to generation.

• Some genes (recessive) are masked by others (dominant).

Mendel’s first Law

• An organism’s characteristics are determined by internal factors which occur in pairs. Only one a pair of such factors can be in the single gamete.

• The characteristics of an organism are controlled by genes occurring in pairs. Of the pair of such genes, only one can be carried in a gamete.

Test cross/ Back cross

A cross between an individual with the phenotype of the dominant characteristic but unknown phenotype

cross with a double recessive

Codominance

both alleles

both alleles in a heterozygote and are expressed individually.

1:2: 1 ratio

Incomplete dominance

heterozygote

the heterozygote phenotype is an intermediate between the two parental genotypes.

Neither of the alleles is completely dominant.

They are described as partially dominant.

So the rule on capitals and lower case to represent the alleles does not apply.

1:2:1

Linkage

gene

CHARATISTICS

where the gene for two characteristics are on the same chromosome.

They cannot segregate separately.

During meiosis they do not separate, because they are on the same physical structure

Why are punnet squares is not used for linkage

crossing over

number of gametees with diff

Crossing over between two given genes is a rare event and does not happen in most cells, so the majority of gametes would still be parental

thus the number of gametes with different genotypes is not equal; ratios are not produced

the further apart 2 genes are on a chromosome, the more opportunity there is for a crossover to occur between them

This leads to a more recombinant gamete and therefore more offspring with recombinant phenotypes

Recognising linkage

If the ratio is not 9:3:3:1

crossover value number of recombinants x100

number of progeny

Sex determination is controlled by

temp

ploidy

• Temperature

• Changes in gender, sequential hermaphroditism.

  • Protandry – start as males

  • Protogyny – start as females.

• Ploidy, In some species some eggs remain unfertilised.

  • Haploid eggs develop into males.

• Diploid eggs develop into females

• Chromosomes structure.

Sex Determination in Humans

• In humans the are 23 pairs of chromosomes.

  • 22 pairs are homologous autosomes.

  • 1 pair are not always homologous, and control sex.

  • These are called sex chromosomes.

  • They are called X and Y

Female and Male mammals

Females are XX. All the female secondary oocytes contain an X chromosome

• All their gametes contain an X chromosomes. called the homogametic sex.

  Males are XY. An X chromosome passes into one secondary spermic sites and a Y chromosome passes into the other

• Half of their gametes contain an X chromosome, half will contain a Y chromosome.

• They can be called the heterogametic sex.

At ertilisation the oocyte may be fertilized by either an X carrying sperm or a Y carrying sperm

with equal probability this gives an equal chance of the fetus being male or female

sex linkage

The X chromosome in mammals is much longer than the Y chromosome.

It contains genes which are not present on the Y chromosome.

These genes are not involved in sex determination.

A gene that is carried by the X or Y chromosome so that a characteristic it encodes for is seen predominately seen in one sex

examples of sex linkage

• Any gene on the X chromosome not found on the Y chromosome is called a sex linked gene. 

• It is inherited with the sex of the individual.

• Examples:

  • Red/green colourblindness

  • Duchenne muscular dystrophy

  • Haemophilia 

haemophillia

 

Phenotype	Genotype	Blood biochemistry
Normal female	XHXH	Factor VIII produced
Carrier female	XHXh	Factor VIII produced
Sufferer female	XhXh	No factor VIII
Normal Male	XHY	Factor VIII produced
Sufferer Male	XhY	No factor VIII

1:1 ratio for both

inheritance of sex linked conditions

• Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations of a protein called dystrophin that helps keep muscle cells intact.

caused by an X-linked recessive allele of the dystrophin gene.

Mutuations

A mutation is a change in the volume, arrangement or structure of DNA of an organism.

Mutations can affect the gene or the chromosome.

They can be:

• spontaneous, without apparent cause

• random, happen with equal probability anywhere

mutations that occur in gametes can be inherited

mutation rate

• Mutations occur during DNA replication and cell division.

  So the shorter the life cycle the greater the rate of mutations.

Mutation rate can be increased by:

• ionising radiation, UV light, X-rays, ~ Radiation causes adjacent pyrimidine bases to join, so that at replication DNA polymerase may insert an incorrect nucleotide

• Mutagenic chemicals eg. polycyclic hydrocarbons. Chemicals eg. acrodine are mutagenic because they have flat molecules which can slide in between base pairs in the double helix and prevent DNA polymerase inserting the correct nucleotide at replication

How mutations can happen

gene or point mutation

chromosome mutation

• Gene or point mutation: DNA is not copied accurately in the S phase, before cell division. these errors involve one or a small number basis

• chromosome mutation: chromosomes may get damaged and break. Broken chromosomes may repair themselves and the DNA and protein rejoin. But they may not repair correctly altering their structure and potentially affecting large number of genes.

How mutations can happen

Aneuploidy

Polyploidy

• Aneuploidy: a whole chromosome or small number of chromosomes may be lost or added (non-disjunction) when a chromosome fails to separate to the poles of dividing cells that anaphase l or when chromatids fail to separate at anaphase ll

• Polyploidy: the number of chromosomes made double if the cell fails to divide following the first nuclear division after fertilization

Result of changes to DNA sequences in a gene

• DNA changes will alter the triplet code 

• The changed triplet code is transcribed into an altered mRNA codon

• altering the amino acid incorporated into the polypeptide chain, hence changing the primary structure. 

• Can change the 3D structure, hence non-functional.

how a gene mutation can occur

• Addition – addition of a base, an extra amino acid is added to the polypeptide chain at translation

• Deletion – loss of base, polypeptide has one fewer amino acid when translated.

• Substitution – the wrong nucleotides are used and replace the correct ones

• Inversion – adjacent bases on the same DNA strand echange position

• Duplication – a section of nucleotides are repeated

the effect of point mutation on the polypeptide produced at translation

a new codon

framshit mutuation

• A new codon may code for the same amino acid so there is no change to the polypeptide, silent mutation

• if an amino acid with a similar chemical nature is substituted, the effect may be small

• if the mutation is at the significant site on the protein molecule it may make a significant difference to the activity of the protein eg.structure of active site would be destroyed

• if one or two bases are added or deleted, a frameshift mutation occurs and all subsequent and may not acids Incorporated will be altered

Sickle cell disease

mrna has a codon

caused by a substitution point mutation in the gene, producing the beta polypeptide chain of haemoglobin.

• Adenine replaces thymine in the DNA

• mRNA has the codon GUG for valine in the mutation instead of the normal GAG for Glutamic acid

the side chain of glutamate is large and hydrophilic whereas valiene is small and hydrophobic when the

Destruction of hemoglobin - sickle cell

within the red blood cells

arrogate

When the oxygen tension is low, the affected hemoglobin within the red blood cell arrogates

the cell membrane collapses on the precipitated hemoglobin and the red blood cell becomes sickle shaped

the cell becomes fragile and may break in the capillaries. Causing blockage in capillaires

Chromosome mutation

Changes in the structure or number of chromosomes in cells

Changes in chromosome structure

prophase 1

Occurs during prophase I of meiosis when homologous chromosomes form chiasmata and the chromatids break and rejoin.

• Deletion: portion of chromosome is lost

• Duplication: Portion of the chromosome is repeated

• Inversion: a portion of chromosome is cut out and inverted before being replaced.. Genotype is unchanged but phenotype may be altered.

• Translocation: portion of chromosome is removed and becomes attached either at a different point on the same chromosome or to a different chromosome

Changes in chromosome numbers

a faulty division

Most likely to occur during meiosis, when homologus chromosome separates at anaphase l or when chromatids separate at anaphase ll

a faulty spindle can result in the chromosomes not being shared equally between daughter cells. The faulty cell division means one of the daughter cells receives two copies of a chromosome while the other gets none.

Non-disjunction

A faulty cell division in meiosis following which one of the daughter cells receives two copies of a chromosome and the other receives none

Down syndrome

Chromosome 21 is affected. If non disjunction happens during ogenisis, a secondary oocyte has either no chromosomes or two copies, instead of one

those with no chromosome 21 cannot produce viable embryo. A secondary oocyte with two copies of C21 that fuses with normal sperm, produces a viable mbryo with cells containing three copies of chromosomes instead of 2.

Called Trisomy 21

Changes in the number of chromosome sets

• An organism with a complete set of chromosomes is called euploid.

• An organism with extra or fewer chromosomes are called aneuploid.

• if they have several sets of chromosomes, there are polyploid

Causes of polyploidy- defect in spindle

A defect in the spindle at meiosis may result in all the chromosomes at anaphase l , or all the chromatids at anaphase ll moving to the same pole of a cell.

This makes gametes with two of each chromosome instead of one. When a diploid gamete is fertilized by a normal haploid gamete, a triploid zygote with three sets of chromosomes is made

It may survive but it will not be able to make a homologous pairs at meiosis

Therefore not be able to make gametes so it will be infertile

Causes of polyploidy

endomitosis

• If two diploid gametes fuse, a tetraploid (4n) is produced

• endomitosis is the replication of chromosomes that is not followed by cytokinesis. If this happens in an early embryo, 4 sets of chromosomes are incorporated into the new nuclear envelope and successive rounds of mitosis continue to produce tetraploid cells.

where polyploidy is common

• Common in plants rare in animals.

• Possibly because:

  • Reproduce asexually

  • Many are hermaphrodite, so don’t use chromosomes to determine sex.

• It seems to increase vigour of the plant.

Colchicine

ARRESTS

• Colchicine is a chemical mutagen that arrests spindle formation and so can lead to polyploidy.

• It is produced in the autumn crocus.

• It is used in plants to produce polyploid plants in plant breeding.

• (It is also used a treatment for some human conditions like inflammation and gout.)

Carcinogen

An agent that causes cancer

Oncogene definition

a gene that has the potential to cause cancer

A proto oncogene with a mutation that results in cancer

tumor suppressor genes

Jeans control cell division and division is halted when enough cells have been produced for growth and repair

Genes that regulate mitosis and prevent cells dividing too quickly are tumor suppressors genes.

Formation of a tumor

COOLECTON

CHARCTOSESSSSSSDDNHM

A mutation may affect one of the tumor suppressor genes and make it lose its regulatory function

the cell could then go through continual repeated mitosis, which characterizes cancer

if the cell is escapes the attack of the immune system it produces a collection of cells called a tumor

TP53

A tumor suppressor gene that codes for protein p53

can't form a mutant form of p53 if there are abnormalities in the tumor suppressor gene

The difference between normal and mutant p53

undergo mit

Normal p53

• activates repair of damaged DNA

• prevents the cell from entering S phase while damaged DNA is repaired

• initiates apoptysis if damage DNA cannot be repaired

Mutant p53

• no DNA repair

• cell with damaged DNA enters S phase and DNA is replicated

• mutant cells survive and undergo mitosis

Oncogenes

A proto oncogene codes for a protein that contributes to cell division

mutation may switch on such a gene permanently so excessive amounts of the protein is made causing rapid, uncontrolled, repeated mitosis (cancer)

Why a proto oncognene may be mutated

a mutation causes

• A mutation causes chromosomes to rearrange and places the proto-oncogene next to a DNA sequence that permanently activates it

• there is an extra copy of the proto-oncogene resulting in too much of its products being made, causing excessive mitosis

Epigenetics control

modifying

The control of gene expression by modifying DNA or histones

but not affecting the DNA nucleotide sequence

Gene expression

• Genes which code for a protein are called cistrons.

• There are other genes which control the switching on and of genes.

switching genes

some transripyion factors

• Some transcription factors in the cell make it easier for the RNA polymerase to attach.

• Effectively the switches the gene on.

• Some transcription factors in the cell block RNA polymerase.

• Effectively the switches the gene off.

Methylation this affects

transcriptiom

blocks binding

• This affects the cytosine in the DNA. 

• Methylation reduces access of the gene to enzymes involved in transcription.

• It blocks the transcription factors from binding to the promotor genes.

Histone modification

• They include:

  • Acetyl groups

  • Methyl groups

  • Phosphate groups.

• Histone proteins are used to organise the DNA in chromosomes

• Histone modification leads to looser coiling making the DNA more accessible to Transcription factors

• This leads to more transcription factors being able to reach the DNA. If the histone coils more tightly this can prevent gene expression.

• Acetylation of histones is known to increase the expression of genes through transcription activation.

totipotency

genes coding for enzyme

• The zygote has a nucleus which can differentiate into all cell types. 

• This is called totipotency.

• However, as the cells start to differentiate they start to switch off genes coding for enzymes that they may no longer need.

• E.g. a skin cell can produce melanin, but not rhodopsin needed by an eye cell.

consequences of epigenetic changes- genomic imprinting

Iif genes are actiavted N gametes

If jeans are in activated in gametes, the inactivation maybe transferred to the next generation

A gene may be permanently switched off by DNA metythalation on the chromosome derived from one parent

If this switching is damaged a medical condition may ensue

Consequences of epigenetic changes- X inactivation

changes may switch

changes can switch off the whole chromosome.

other x chromsome is inactivated and becomes a ass of densely staining chromatin- Barr Body