The Chromosomal Basis of Inheritance

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1 The Chromosomal Basis of Inheritance

2 Factors and Genes Mendel s model of inheritance was based on the idea of factors that were independently assorted and segregated into gametes We now know that these factors are actually genes that are located on chromosomes

3 Concept 15.1 Mendelian inheritance has its physical basis in the behaviour of chromosomes Mendel s laws of segregation and independent assortment can be accounted for by the behaviour of chromosomes during meiosis Morgan s experiments with Drosophila provided the first evidence that specific genes are associated with specific chromosomes

4 Genes and Chromosomes Even after chromosomes were visualized and observed through microscopy, there were no indications that Mendel s factors were related to the chromosomes It was only in the early 1900s when scientists noticed similarities between meiosis and Mendel s model Chromosome Theory of Inheritance Genes have specific loci (positions) along chromosomes Chromosomes undergo segregation and independent assortment

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6 Thomas Hunt Morgan Morgan conducted experiments with Drosophila melanogaster (fruits flies) Drosophila have many offspring and only 4 pairs of chromosomes He mated many pairs of Drosophila until a mutant trait (different from the common wild type) was found in a male fly that had white eyes as opposed to the common red eyes. This fly was then mated to red eyed females

7 P generation female (wild-type eyes) X male (mutant eyes) F1 generation All offspring display wild-type phenotype F2 generation Offspring exhibit a 3:1 ratio of wild-type to mutant eyes

8 Results similar to Mendel`s data with pea plants. However, only males displayed the white eyed phenotype. Possibility of correlation with sex chromosome.

9 Concept 15.2 Sex-linked genes exhibit unique patterns of inheritance Sex chromosomes determine sex Sex-linked genes on sex chromosomes have a unique pattern of inheritance

10 The Chromosomal Basis of Sex The X-Y System Human sex chromosomes are known as the X- chromosome and Y-chromosome The Y-chromosome is the smaller chromosome, with the shorter arms containing regions that are homologous to regions of the X-chromosome. XX develops as a female, XY develops as a male Therefore, the male gamete determines the sex of the offspring with a fifty-fifty chance (X to for a female and Y for a male)

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12 Inheritance of Sex-Linked Genes A sex-linked gene is a gene on a sex chromosome Although a gene appears on a sex chromosome, it is not necessarily related to sex determination or sex characteristics If a recessive sex-linked trait is on the X- chromosome, a female must be homozygous recessive for the trait to display the phenotype. Alternatively, a male only has one copy of the X- chromosome. Therefore there is no possibility to be heterozygous for that gene. Examples: colour blindness, hemophilia

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14 X Inactivation in Female Mammals While females have two X-chromosomes, they do not make double of the proteins coded for by the X-chromosomes In each cell, one of the X-chromosomes will become inactivated through DNA methylation This inactive X-chromosome condenses into a Barr body that remains near the nuclear envelope The X-chromosome that is inactivated in each cell is random, meaning that each female has a mosaic of two cell types

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16 Concept 15.3 Linked genes tend to be inherited together because they are located near each other on the same chromosome Mendel s law of independent assortment dictates that genes segregate independently of each other. However, genes that are closer together do not always sort independently and are considered linked Recombination frequencies between genes can be used to map genes on a chromosome

17 Chromosomes and Linked Genes Each chromosome has hundreds or thousands of genes Linked genes are genes located on the same chromosome that tend to be inherited together These linked genes cause deviations from the expected outcome of Mendel s law of independent assortment.

18 How Linkage Affects Inheritance In Mendel s experiments, he observed that some offspring have combinations of traits that do not match either parent in the P generation We now know this is due to crossing over of chromosomes during meiosis Gametes from yellow-round heterozygous parent (YyRr) YR yr Yr yr Gametes from greenwrinkled homozygous recessive parent (yyrr) yr YyRr yyrr Yyrr yyrr Parentaltype offspring Recombinant offspring

19 How Linkage Affects Inheritance In Morgan s experiments, inheritance of certain traits were found to deviate from Mendel s law of independent assortment. For the characteristics of body colour and wing type, there are two observable phenotype. The wild-type phenotypes are grey bodies and normal-sized wings. The mutant phenotypes are black bodies and small vestigial wings. Morgan found a higher proportion of parental phenotypes than would be expected from independent assortment

20 Cross between two flies that are true-breeding for two different genes that follow a two-allele complete dominance mode of inheritance.

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22 Recombination The offspring that show new combinations of the parental traits are known as recombinant offspring If 50% of all offspring are recombinants, then there is a 50% frequency of recombination. Based on his results, Morgan proposed that some process must occasionally break the physical connection between genes on the same chromosome This process is the mechanism of crossing over which occurs between homologous chromosomes

23 Linked Genes The further apart genes are, the more likely they are to assort independently and recombine in new combinations during crossover. If the frequency of recombinants is less than 50%, the genes are likely linked (closer together on the same chromosome).

24 Mapping the Distance Between Genes Using Recombination Data After the discovery of linked genes and recombination due to crossing over, one of Morgan s students came up with a method for constructing a genetic map. Genetic map - An ordered list of the genetic loci along a particular chromosome. Linkage map A genetic map based on recombination frequencies His prediction: The farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency

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27 Concept 15.4 Alterations of chromosome number or structure cause some genetic disorders Nondisjunction during meiosis can result in abnormal chromosome number Chromosomal breakage can result in abnormal chromosome structure Chromosomal abnormalities can lead to various disorders

28 Abnormal Chromosome Number Nondisjunction Error in segregation of homologous chromosomes or sister chromatids during meiosis

29 Abnormal Chromosome Number Aneuploidy Zygote produced with an abnormal number of chromosomes Monosomic missing chromosome in an aneuploid zygote Trisomic extra chromosome in an aneuploidy zygote Polyploidy extra chromosome set in an aneuploid zygote

30 Alterations of Chromosome Structure Deletion removes a chromosomal segment Duplication repeats a chromosomal segment Inversion reverses a chromosomal segment

31 Alterations of Chromosome Structure Translocation moves a chromosomal segment from one chromosome to a nonhomologous chromosome Reciprocal translocation segments are exchanged Nonreciprocal translocation one direction, no exchange

32 Human Disorders Due to Chromosomal Alterations Down Syndrome (Trisomy 21) Resulting from an extra copy of chromosome 21 (usually fro nondisjunction during meiosis I) Frequency increases with age of the mother Symptoms include characteristic facial features and stature, heart defects and mental delay Prone to other diseases

33 Human Disorders Due to Chromosomal Alterations Aneuploidy of Sex Chromosomes Nondisjunction of sex chromosomes causing either an extra sex chromosome or a missing sex chromosome Klinefelter syndrome (genotype XXY) Male sex organs (though sterile) but may show female secondary sex characteristics Males with an extra Y (XYY) No real distinguishing features Females with trisomy X (genotype XXX) No real distinguishing features Turner syndrome (genotype X0) Phenotypically female but sterile. Need hormone therapy to development secondary sex characteristics

34 Human Disorders Due to Chromosomal Alterations Disorders caused by structurally altered chromosomes (deletions, translocations, etc.) Cri du chat Results from a specific deletion in chromosome 5 Symptoms include mental retardation, unusual facial features, a cat-like cry Early death Chronic myelogenous leukemia Reciprocal translocation (between chromosome 22 and 9) during mitosis of cells that are precursors to white blood cells

35 Concept 15.5 Some inheritance patterns are exceptions to the standard chromosome theory Genomic imprinting can inhibit certain alleles during gamete production, which then leads to relationships between allele expression and parental lineage (maternal or paternal) Extranuclear genes are usually passed on maternally through the cytoplasm and its contents

36 Genomic Imprinting Occurs during the formation of gametes and results in the silencing of one allele of certain genes Occurs differently in males and females so that either the alleles are imprinted in the egg, or in the sperm Therefore, only one allele is expressed for each imprinted gene, either male or female

37 Genomic Imprinting Imprinted alleles usually have alterations such as a methylation of cytosine nucleotides However, methylation can also result in activation of expression of an allele Affects only a small number of genes Not the same as sex-linked alleles

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39 Inheritance of Organelle Genes Extranuclear genes exist outside the nucleus They can be found in organelles such as mitochondria or chloroplasts Theses organelles are obtained from the egg and therefore the offspring will inherit these specific extranuclear genes from the maternal source

40 Extranuclear gene disorders Mitochondrial myopathy Weakness, intolerance of exercise, muscle deterioration Leber s hereditary optic neuropathy Sudden blindness in 20s or 30s Possible connection to may other disorders

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