2Figure 15.1 The chomosomal basis of Mendel’s laws REVIEW OF MENDEL’S DISCOVERIES:The arrangement of chromosomes at metaphase 1 of meiosis and their movement during anaphase 1 account for the segregation and independent assortment of the alleles for seed color and shape.Let’s look at figure 15.1 on text page 270 together!REMEMBER:Principle of Segregation: during the formation of gametes, the two traits (alleles) carried by each parent separate.Principle of Assortment: States that each allele pairs of different genes segregates independently during gamete formation – applies when genes for two characteristics are located on different pairs of homologous chromosomes.The arrangement of chromosomes at metaphase 1 of meiosis and their movement during anaphase 1 account for the segregation and independent assortment of the alleles for seed color and shape.2
3Beyond Mendel: Thomas Morgan Thomas Morgan was the first scientist to associate a specific gene with a specific chromosome, early in the 20th century.Morgan chose to work with fruit flies (Drosophila melanogaster), because:They are prolific breeders – a single mating will produce hundreds of offspringA new generation can be bred every two weeksThey have only four chromosomes – easily distinguishable with a light microscopeThey have three pairs of autosomes and one pair of sex chromosomesThese characteristics make the fruit fly a convenient organism for genetic studies!
4Normal v/s Mutant Traits The normal phenotype for a character (most common in natural populations) is referred to as WILD TYPE.Traits that are alternatives to the wild type are called MUTANTS – because they are due to alleles assumed to have originated as changes in the wild-type allele.
5Morgan – Tracing a Gene to a Specific Chromosome in Drosophila Wild-type Drosophila flies have red eyes (bottom).Morgan discovered a mutant male with white eyes (top).This variation made it possible for Morgan to trace a gene for eye color to a specific chromosome.Figure 15.3
6Sex-Linked Inheritance When Morgan bred his mutant male to a wild-type female, all F1 offspring had red eyes. The F2 generation showed a typical Mendelian 3:1 ratio of traits, but the recessive trait – white eyes – was liked to sex.All females had red eyes, but half the males had white eyes. Morgan hypothesized that the gene responsible was located on the X chromosome and that there was no corresponding locus on the Y chromosome.
7Linked GenesNumber of genes in a cell is FAR greater than the number of chromosomes.Linked Genes are genes that are located on the same chromosome and that tend to be inherited together .Inheritance patterns with linked genes tend to deviate from expected Mendelian ratios:Morgan was the first to trace a gene to a specific chromosome.Sex-linked genes are genes located on a sex chromosome (X or Y chromosome).
8EVIDENCE FOR LINKED GENES IN DROSOPHILA Figure 15.9EVIDENCE FOR LINKED GENES IN DROSOPHILAThis example explains that body color AND wing size must be linked – look at the expected v/s observed ratios in the offspring!Pages 293The tinted area highlights a testcross between a dihybrid female fly, heterozygous for both body color and wing size, and a double-recessive male, homozygous for both recessive alleles (the male is a “double mutant” phenotype). When Morgan “scored” (classified according to phenotype) 2300 offspring from such matings, he observed a much higher proportion of parental phenotypes than would be expected if the two genes assorted independently. Morgan concluded that these genes are usually transmitted together because they are located on the same chromosome. Crossing over accounts for the recombinant phenotypes (combinations of traits different from the combination in either parent).8
9Morgan determined that Genes that are close together on the same chromosome are linked and do not assort independentlyUnlinked genes are either on separate chromosomes of are far apart on the same chromosome and assort independentlyParentsin testcrossb+ vg+b vgb+ vg+b vgb vgMostoffspringXor
10Genetic Recombination Genetic Recombination is the general term for the production of offspring with new combinations of traits inherited from two parentsOrganisms that have these are called “recombinants”“parental types” would be offspring that phenotypically match either parent
11Figure 15.5a Recombination due to crossing over In crossing over during prophase of meiosis I, chromatids of paired homologous chromosomes break, and homologous chromatid fragments switch places…crossing over. This creates recombinant chromosomes.NOTICE the parental types and the recombinants created during Meiosis I in the diagram above.In crossing over during prophase of meiosis I, chromatids of paired homologous chromosomes break, and homologous chromatid fragments switch laces…crossing over. This creates recombinant chromosomes.11
12Figure 15.5b Recombination due to crossing over If we follow the recombinant chromosomes through fertilization of the ova by the sperm of genotype b vg, we see that they give rise to some recombinant offspring, with genotypes and phenotypes different from either of their parents. The recombinant frequency is the percentage of recombinant flies in the total pool of offspring.12
13Mapping Genetic LociGenetics can use recombination data to map a chromosome’s genetic loci!Method discovered by Alfred SturtevantCalled a genetic map: an ordered list of the genetic loci along a particular chromosome.A linkage map is a genetic map based on recombination frequencies.Assuming that cross-over possibility is approximately equal at all points on a chromosome, the further apart two genes are, the HIGHER the probability that a cross-over will occur between those two genes – the higher the recombination frequencyREASONING: the greater the distance between two genes, the more points there are between them where crossing over can occur.The distances between genes are called Map units, or centimorgans in honor of Thomas Hunt Morgan.Equivalent to a 1% recombination frequency.
14Figure 15.6 Using recombination frequencies to construct a genetic map The probability of a crossover between two genetic loci is proportional to the distance separating the loci. The distances between genes is expressed in map units, defining one map unit as equivalent to a 1% recombination frequency (also called a centimorgan in honor of Morgan).b = body colorcn = cinnabar eyes (brighter red)vg = wing sizeThe probability of a crossover between two genetic loci is proportional to the distance separating the loci.14
15Figure 15.7 A partial genetic map of a Drosophila chromosome This simplified map shows just a few of the genes that have been mapped on Drosophila chromosomes II.Notice that more than one gene can affect a given phenotypic characteristic, such as eye color.
16Constructing a Linkage Map Determine the sequence of genes along a chromosome based on the following recombination frequencies:A-B = 8 map unitsA-C = 28 map unitsA-D = 25 map unitsB-C = 20 map unitsB-D = 33 map unitsANSWER:D-A-B-C
17The Sex ChromosomesIn humans and other animals, there are two varieties of sex chromosomes: X and Y.XX = girlXY = boyAnatomical signs of sex begin to emerge in humans when the embryo is about 2 months old.Before then, the rudiments of gonads are generic – they can develop into either ovaries or testes, depending on hormonal conditions within the embryo.Y chromosome must be present to produce testes.
18Sex-Linked (x-linked) Genes Show up more often in the sex that has only one copy of the X- chromosome!Fathers pass sex-linked alleles to all of their daughters but none of their sons.Mothers can pass sex-linked alleles to both sons and daughters.If a sex-linked trait is due to a recessive allele, a female will express the phenotype only if she is homozygous. BUT, a male receiving the recessive allele from his mother will ALWAYS express the trait – because his other allele is the Y chromosome!Human examples of sex-linked disorders:Duchenne muscular dystrophyHemophiliaBaldnessREFER STUDENTS TO FIGURE 15.7 ON PAGE 291.
19Sex-linked genes follow specific patterns of inheritance Figure 15.10a–cXAXAXaYXaYXAXaXAYXAYaXAOvaSpermXaYAXaYaA father with the disorder will transmit the mutant allele to all daughters but to no sons. When the mother is a dominant homozygote, the daughters will have the normal phenotype but will be carriers of the mutation.If a carrier mates with a male of normal phenotype, there is a 50% chance that each daughter will be a carrier like her mother, and a 50% chance that each son will have the disorder.If a carrier mates with a male who has the disorder, there is a 50% chance that each child born to them will have the disorder, regardless of sex. Daughters who do not have the disorder will be carriers, where as males without the disorder will be completely free of the recessive allele.(a)(b)(c)
20X-Inactivation in Female Mammals Only one X chromosome stays active in females – the other becomes inactivated during embryonic development.The inactive X in each cell of a female condenses into a compact object – a Barr BodyBarr body chromosomes are reactivated in the ovary cells that give rise to ova.See page and discussion of tortoiseshell cat.XIST is a gene that is active ONLY on the Barr-body chromosome.
21Figure 15.10 X inactivation and the tortoiseshell cat Mary Lyon and the inheritance of inactivation: page 292If a female is heterozygous for a particular gene located on the X chromosomeShe will be a mosaic for that character
22MutationsMutations are changes in DNA that also change the protein produced.Can happen spontaneously (no reason they occurred).-OR-By mutagens – substances or agents that can cause changes in DNAEx. Chemicals, radiation, x-rays, viruses
23“Unseen” ChangesChanges can occur without the organism showing an effect!NOTE: changes DO occur that are not true “mutations” – protein production not affectedThese occur in the INTRON areas of chromosomes, and as long as the length of the code is not affected, they will not be seen in the organism…
24Mutations in Reproductive Cells Changes in reproductive cells:code is changed in sperm or eggwon’t effect the parent, but CAN effect the offspring produced from those altered sex cellscan be POSITIVE – new, adaptive traits
25Mutations in Body Cells Changes in body cells:Are not passed on to offspring, but can cause MAJOR complications for the individual effectedEx. Solar radiation – skin cancerAgain the process is thought to be cumulative effect of exposure to mutagens over time.
26Point Mutation v/s Chromosomal Mutation Point Mutation: change in a single base pair of DNA.Chromosome Mutation: change in a large portion of an entire chromosome – effects MANY genes.
27Point Mutations Point mutation: change in single base pair of DNA if the mutation does not effect the length of the code, it will just change the amino acid in that positionEx: SUBSTITUTIONIf the mutation does change the length of the code, is called a frameshift mutation, and are two types:Ex: INSERTIONS AND DELETIONS
28Figure 15.13 Alterations of chromosome structure deletion – part of chromosome is broken off and lost completelyduplication – broken fragment of chromosome attaches to sister chromatid so that section is repeated on that chromatidinversion – when fragment reattaches to original chromosome but in reverse ordertranslocation – broken fragment attaches to a nonhomologous chromomosome(can exist as reciprocal or nonreciprocal)
29Gene Mutations – Effect Only ONE Base in the Code Examples: Substitutions, Insertions, DeletionsGene Mutations only affect ONE point of the code -- often called Point Mutations
30Chromosomal Mutations Can effect chromosome number AND chromosome shape:Mistakes in numbers of chromosomes such as nondisjunction (where members of a pair of homologous chromosomes do not move apart properly resulting in offspring that have):Aneuploidy – abnormal chromosome number – can be (Trisomy or Monosomy or Polyploidy)
31Figure 15.11 Meiotic nondisjunction Either type of meiotic error will produce gametes with an abnormal chromosome number.Either type of meiotic error will produce gametes with an abnormal chromosome number.31
32Trisomy 21 – Down Syndrome Karyotype showing trisomy 21 – individual has three #21 chromosomes. Child will exhibit facial characteristics of Down syndrome.
33Trisomy 16 – Major Cause of Miscarriage in 1st Trimester Pregnancy
34Monosomy X – Turner Syndrome XO individuals are phenotypically female, but their sex organs do not mature at adolescence, and they are sterile. Most have normal intelligence.
35XXY – Klinefelter Syndrome XXY – Klinefelter Syndrome – have male sex organs, but testes are abnormally small and the man is sterile. Often includes breast enlargement and other feminine body characteristics.
36Figure 15.x3 XYY karyotypeMales XYY – not characterized by a particular syndrome, but usually are somewhat taller than average.
37Fragile X SyndromeNamed for the physical appearance of an abnormal X chromosome, the tip of which hangs on to the rest of the chromosome by a thin thread of DNA.Mental retardation – more common in males and usually inherited by Mother.
38Human Genetic Anomalies Autosomal Dominant Genes – body cells, not passed on to offspringAutosomal Recessive Genes – body cells, not passed on to offspringX-linked recessive Genes – sex cells, passed on to offspringY-linked – only in malesChromosomal Abnormalities – if affects sex chromosomes, passed on to offspringMultifactorial – genetic component (gene or chromosome) plus a significant environmental influenceMitochondrial DNA comes from Mom – maternal inheritance, because mitochondria passed on by zygote all come from the cytoplasm of the ovum