genetics: inheritance-> disease

why is genetics relevant (5)

personalised medicine

genetic engineering and gene therapy

conservation genetics

forensics

agricultural and crop manipulation

what is genetics

study of heredity and variation

heredity

transmission of traits from one generation to the next

hereditary variation

the occurrence of dissimilar traits among generations

gene

hereditary unit comprising coded information passed to offspring

gametes

reproductive cells that transmit genetic information from one generation to the next

somatic cells

all cells in the body except the gametes

dex chromosomes

chromosomes responsible for determining the dex of an individual

autosomes

all other chromosomes

diploid cell

any cell with 2 chromosome sets

haploid cell

any cell that contains single set of chromosomes

molecular genetics

study and structure and function of genes at molecular level

sequence of steps in polymerase chain reaction cycle (PCR)

denaturation→ annealing→ extension

genomics

study of whole sets of genes and their interactions

shotgun sequencing (2)

cloning and sequencing of fragments and ordering them relative to each other

once order of sequences has been worked out, the entire sequence for an individual chromosome is obtained

human genome project- technology used (3)

recombinant DNA

PCR

sanger sequencing

human genome project- goals (2)

determine the sequences of the 3 billion chemical base pairs that make up human DNA

identify all approx 20,000-25,000 genes in human DNA, store in databases to improve tools for data analysis

human genome project- results (4)

human genome contains 3.2 billion bases

average gene length→ 3000 bases

largest gene dystrophin→ 2.4 million base pairs

1.5% genome is coding

human genome project- medical implications

particular gene sequences associated with numerous diseases and disorders, such as breast cancer, muscle disease, deafness and blindness

DNA fingerprinting uses (3)

identify different species of bacteria and fungi

forensics

paternity testing and other family relationships

transgenics

transgenic organism carries genes introduced using molecular techniques such as gene cloning, also called Genetically Modified Organisms (GMOs)

gene therapy- gene editing (3)

eg Acute lymphoblastic leukaemia

remove immune cells from patients body, genetically engineer them to attack cancerous cells

program T-cell to seek out and kill andy cells with protein CD19 on surface

CRISPR-Cas technology (2)

Jennifer Doudna and Emmanuelle Charpentier

“the ability to cut DNA where we want to has revolutionised the life sciences”

gregor mendel

father of genetics

what plant did mendel work on

garden pea Pisum sativum

character

heritable feature that varies among individual

trait

each specific variant of a character

true breeding

offspring of self pollinating individuals have the same traits as parents

P generation

true breeding parental generation

F₁ generation

first generation of offspring of hybridisation

F₂ generation

generation arising from allowing F₁ hybrids to self pollinate or cross pollinate with other F₁ hybrids

genotype

genetic makeup of organism

phenotype

observable expression of the genotype

mendels experiments

crossed pea plants with different traits and discovered that parents pass discrete heritable factors (genes) to offspring

mendels methods (2)

started experiments with true breeding varities

studied distinct “either-or” characteristics, such as white or purple flowers

mendels hybridisation experiments

steps 1 & 2: allowed him to control pollination

steps 3 & 4: seeds developed and planted

step 5: F1 generation grew and characters recorded

crossed white and purple flower, but F1 generation only had purple

he then bred F1 hybrids, some of the F2 generation were white, confirms particulate theory of inheritance

Mendel’s law of segregation (3)

• each organism contains two factors for each trait

• the factors segregate during the formation of gametes so that each gamete contains only one factor from each pair of factors

  • when fertilisation occurs, the new organism will have two factors for each trait, one from each parent

four concepts behind law of segregation (4)

1. the variation observed in inherited characters due to different versions of same gene

2. for each character, an organism inherits two alleles, one from each parent

3. if the two alleles for a gene differ, the dominant allele determines the organisms appearance and the other (recessive allele) has no noticeable effect on appearance

4. the two alleles segregate (separate out) during gamete production

testcross

breeding individual of unknown genotype with homozygous recessive individual

Mendel’s law of independent assortment

alleles of different genes assort independently of each other during gamete formation

complete dominance

phenotypes of heterozygote and dominant homozygote are indistinguishable eg pea shape, recessive not apparent in heterozygote

codominance

both alleles effect the phenotype in separate, distinguishable ways. neither allele in heterozygote is dominant over the other instead both expressed equally in phenotype

incomplete dominance

heterozygote is intermediate between both homozygous states

way of describe alleles in incomplete dominance, eg in carnations

C^R : red colour (homozygote C^RC^R)

C^W: white colour (homozygote C^WC^W)

heterozygote C^RC^W: intermediate (pink) colour

pleiotropy

a single gene with multiple effects in an organism eg sickle cell

multifactorial conditions

where the condition is governed by more than a single locus

recessive disorders- albanism

inability to produce required amounts of melanin

recessive disorders- alkaptonuria

deficiency in homogentisate oxidase gene

recessive disorders- cystic fibrosis

deficiency in cystic fibrosis conductance regulator gene (CFTR)

recessive disorders- Tay- Sachs (2)

deficiency in hexoseaminidase- A (hexA) gene— metabolic enzyme

The lack of this enzyme (HEXA) results in a ganglioside accumulation in the lysosomes and swelling in many tissues, most notably neurons.

dominant disorders- achondroplasia

caused by mutation in the fibroblast growth factor receptor-3 gene

dominant disorders- huntingtons disease

located on tip of chromosome 4

sex linked disorders- duchenne muscular dystrophy (2)

occurs in boys, X linked recessive pattern of inheritance

result of mutations in huge gene that encodes dystrophin

sex linked disorders- haemophilia

results in missing or abnormal plasma proteins needed to form a clot

euploid

normal number of chromosomes

polyploid

3 or more sets of chromosomes

non disjunction (2)

occurs when problems with meiotic spindle causes an error in daughter cells

one gamete receives 2 of the same chromosome and another gamete receives no copy

chromosomal disorders- klinfelter syndrome

when an egg bearing two X chromosomes fertilised by Y (XXY)

chromosomal disorders- Turner syndrome

sex chromosome aneuploidy, X chromosome but no Y (X)

chromosomal disorders- XYY males

results in fertile males of normal appearance

chromosomal disorders- down syndrome

3 copies of chromosome 21

Thomas Hunt Morgan—- Drosophila (4)

studied fruit fly Drosophilia melanogaster

demonstrated that genes found on chromosomes

• all F1 hybrids wild type (red eyes), red dominant over white

• only males had white eye trait— allele linked to sex of fly

1909—-Archibald Garrod (2)

genetic factors dictate/ control phenotype though enzymes which catalyse specific reactions in a cell

inherited disorders due to persons inability to make particular enzyme

1930s—-George Beadle and Boris Ephrussi (2)

white eye mutant of Drosophilia due to lack of the enzymes

direct evidence came from George beadle and Edward tatum working with bread mould Neurospora crassa

1928—Frederick Griffith (4)

first evidence DNA was genetic material

worked with Streptococcus pneumoniae, used S strain (smooth)[smooth capsule that protects from animals defence system— pathogenic] and R strain (rough)[lack capsule—-non pathogenic]

living R bacteria transformed into pathogenic S bacteria by unknown heritable substance from dead cells

transformation: change in genotype and phenotype due to assimilation of external DNA by a cell

1944—- Avery, McCarty and MacLeod

found of all cell contents, only DNA could transform bacteria

1952— Alfred Hershy and Martha Chase (7)

additional evidence for DNA being genetic material using Bacteriophages

The pellet contains the infected bacteria.

The radioactivity of both pellets were measured and only the pellet from the 32P labelled DNA was detected.

Results demonstrate that it was only DNA that was injected into the bacteria.

No 35S labelled protein was detected in the pellet, only in liquid indicating that protein did not enter the bacteria.

When the bacteria were cultured 32P T2 phages were obtained.

It is DNA and not protein that is the genetic material

1948—-Erwin Chargaff (2)

DNA base composition varies from species to species, and within one species varies little

also found A=T G=C Chargaff’s rule

Rosalind Franklin

X ray diffraction photo of DNA molecule

Waston and Crick (1954) were able to work out width, structure of DNA and that it was double helix

Meselson and Stahl experiment

Data is only consistent with semiconservative model of DNA replication ( Watson and cricks model)