1、Basis of GeneticsGenetics-“origin”, a discipline of biology, is the science of heredity and variation in living organisms. The fact that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding. The modern sci

2、ence of genetics, which seeks to understand the process of inheritance, only began with the work of Gregor Mendel in the mid-nineteenth century. Although he did not know the physical basis for heredity, Mendel observed that organisms inherit traits in a discrete mannerthese basic units of inheritanc

3、e are now called genes. DNA, a molecule composed of a chain of four different types of nucleotidesthe sequence of these nucleotides is the genetic information organisms inherit. Adenine (A), Cytosine (C), Guanine (G), Thymine (T). DNA Double HelixHistonesChromatidsTelomereCentromereTelomereNuclearNu

4、cleosome1 Blending inheritance: the idea that individuals inherit a smooth blend of traits from their parents. 2 Inheritance of acquired characteristics: the belief that individuals inherit traits strengthened by their parents3 Other theories included the Pangenesis of Charles Darwin (which had both

5、 acquired and inherited aspects) and Francis Galtons reformulation of pangenesis as both particulate and inherited.History Mendelian and classical genetics Mendel began studying plant breading by trying to find the effects of crossing different strains of common garden pea (Model organism) He carrie

6、d out his research with more precision than had yet been used. He also used the new science of statistics to analyse the results of his experiments. This use of mathematics to describe biological phenomena was a new concept. Mendel did his pioneering work from 1856 to 1865 and his results were publi

7、shed in one paper (reports) in 1866. With the lack of communication at those times, it is not surprising that his work went unnoticed until 1900 when another group if scientists repeated the experiments and then found that Mendel had already developed the ideas some 40 years previous. Out of Mendels

8、 work came two Laws of inheritance:1) Mendel proposed that heredity was controlled by paired factors that segregated when gametes formed and rejoined at fertilisation and,2) The principle of independent assortment indicates that the segregation of one pair of factors, or Alleles, has no influence ov

9、er the way any other pair segregates.The ExperimentsMendel used 34 true-breeding strains of the common garden pea for his experiments. These strains differed from each other in very pronounced (visible) ways so that there could be no doubt as the results of a given experiment. Pea plants were perfec

10、t for such experiments since their flowers had both male (anthers) and female (pistils) flower parts and the flower petals never open therefore no foreign pollen could enter and back crosses (self fertilisation) was easy.Mendel used seven different pairs of traits:1) Seed form - round or wrinkled.2)

11、 Colour of seeds - yellow or green (contents).3) Colour of seed coat white or grey.4) Colour of unripe seedpods - green or yellow.5) Shape of ripe seedpods - inflated or constricted between seeds.6) Length of stem - short 9 - 18 inches of long 6 - 7 feet.7) Position of flowers - axial (on stem) or t

12、erminal (at tip of stem).An Example ExperimentThe Monohybrid CrossIf we take one of Mendels traits e.g. seed colour, yellow vs. green and breed yellow x yellow we will always get yellow, or green x green will always give green. This is then described as true breeding plants.When Mendel crossed a tru

13、e breeding yellow seed plant with a true breeding green seed plant he obtained all yellow seed!E.g.yellow x green Parental Generationall yellow F1 Generation (first filial).Whatever the factor that caused the yellow colour it was more powerful than the factor for green colour. Mendel said that the y

14、ellow factor dominated the green factor.We now recognise that these factors are Alleles genes with slightly different instructions on homologous chromosomes and that one allele is dominant to the otherTherefore the Y yellow allele is said to be the dominant allele while the y which is covered up is

15、said to be the recessive allele. GenotypesHomozygous: This genotype is one in which the alleles on homologous chromosomes are the same.E.g. YY homozygous dominantyy homozygous recessiveHeterozygous: This genotype is one in which the alleles on the homologous chromosomes are different.Eg. Yy = hetero

16、zygousTherefore our true breeding plants must have been homozygous. The resulting F1 generation were heterozygous.Mendels First LawThe factors of inheritance are paired and segregated when gametes are formed. Mendels principal of segregation. We know of homologous chromosomes, alleles and meiosis, a

17、ll of which explains Mendels results.The Experiment Continued . . .The F1 generation is allowed to self fertilize:Yellow X YellowF1 Generation3/4 Yellow : 1/4 Green F2 GenerationInheritance of Two Traits at Once The Dihybrid CrossIf two traits are inherited simultaneously how is the pattern determin

18、ed?Take Yellow vs. Green seed colour and round (smooth) vs. wrinkled seed coat. Round seed coats are found to be dominant over wrinkled seed coats.When a true breeding Yellow - round seed plant is crossed with a true breeding green - wrinkled seed plant all of the first generation are Yellow - Round

19、 seed plants!Therefore, each pair of homologous chromosomes pairs and separated independently of all the others therefore, the two traits segregate independently of each other.This principle is Mendels second law. The law of Independent Assortment.Phenotypic ResultsMendel found that 9/16s of the F2

20、generation where Yellow - Round. 3/162 were Yellow - wrinkled, 3/16s were Green and Round and 1/16 were green and wrinkled.The Test CrossThis is a method of determining whether dominant individual is homozygous or heterozygous. For example if Round = R and wrinkled = r is this individual Round RR or

21、 Rr, since both look (Phenotype) round? The test cross is to breed the unknown genotype R- with a homozygous recessive rr!Test CrossAfter the rediscovery of Mendels work, scientists tried to determine which molecules in the cell were responsible for inheritance. In 1910, Thomas Hunt Morgan argued th

22、at genes are on chromosomes, based on observations of a sex-linked white eye mutation in fruit flies. In 1913, his student Alfred Sturtevant used the phenomenon of genetic linkage to show that genes are arranged linearly on the chromosome.Genetic linkage occurs when particular genetic loci or allele

23、s for genes are inherited jointly. Genetic loci on the same chromosome are physically connected and tend to stay together during meiosis, and are thus genetically linked. This is called autosomal linkage. Alleles for genes on different chromosomes are usually not linked, due to independent assortmen

24、t of chromosomes during meiosis.Chromosomal crossover (or crossing over) is the process by which two chromosomes pair up and exchange sections of their DNA. This often occurs during prophase 1 of meiosis in a process called synapsis. Genetic Consequences Of Meiosis1. Reduction of the chromosomal num

25、ber 2. Segregation of alleles3. Random assortment of the homologs4. bination The common fruit fly (Drosophila melanogaster) is a popular model organism in genetics research A model organism is a species that is extensively studied to understand particular biological phenomena, with the expectation t

26、hat discoveries made in the organism model will provide insight into the workings of other organisms. In particular, model organisms are widely used to explore potential causes and treatments for human disease when human experimentation would be unfeasible or unethical. Escherichia coli Budding yeas

27、t tobacco mosaic virus Arabidopsis thaliana Maize Caenorhabditis elegans Mutations are changes to the nucleotide sequence of the genetic material of an organism. 1. Point mutation Silent mutation Missense mutation Nonsense mutation2. Insertion3. Deletions 1. Point mutations, often caused by chemical

28、s or malfunction of DNA replication, exchange a single nucleotide for another. Most common is the transition that exchanges a purine for a purine (A G) or a pyrimidine for a pyrimidine, (C T). 2. Insertions add one or more extra nucleotides into the DNA. They are usually caused by transposable eleme

29、nts, or errors during replication of repeating elements. 3. Deletions remove one or more nucleotides from the DNA FrameshiftBy effect on functionLoss-of-function mutations are the result of gene product having less or no function. Gain-of-function mutations change the gene product such that it gains

30、 a new and abnormal function. Dominant negative mutations have an altered gene product that acts antagonistically to the wild-type allele. These mutations usually result in an altered molecular function (often inactive) and are characterised by a dominant or semi-dominant phenotype. Lethal mutations

31、 are mutations that lead to the death of the organisms which carry the mutations. A back mutation or reversion is a point mutation that restores the original sequence and hence the original phenotype.Pedigree chartsInheritance of quantitative traits or polygenic inheritance refers to the i n h e r i

32、 t a n c e o f a p h e n o t y p i c characteristic that varies in degree and can be attributed to the interactions between two or more genes and their environment. Though not necessarily genes themselves, quantitative trait loci (QTLs) are stretches of DNA that are closely linked to the genes that

33、underlie the trait in question. Adult onset diseasesDiabetes MellitusCancerEpilepsy a hypertension Ischaemic heart disease Manic depression Schizophrenia Epigenetics refers to changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence,

34、 hence the name epi- (Greek: over; above) -genetics DNA methylation and chromatin remodeling 1. The first way is post translational modification of the amino acids that make up histone proteins. 2. The second way is the addition of methyl groups to the DNA, at CpG sites, to convert cytosine to 5-methylcytosine. RNA transcripts and their encoded proteins Epigenetic effects in humans Genomic imprinting and related disorders Transgenerational epigenetic observations Cancer and developmental abnormalities Twin studies Recent studies invol