NOTES: Ch 15 - Chromosomes, Sex Determination & Sex Linkage

Overview: Locating Genes on Chromosomes ● A century ago the relationship between genes and chromosomes was not obvious ● Today we can show that genes are located on chromosomes ● The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene

The Chromosome Theory of Inheritance states that: ● Mendelian genes have specific loci (positions) on chromosomes ● It is the chromosomes that undergo segregation and independent assortment!

P Generation Yellow-round seeds (YYRR) Green-wrinkled seeds (yyrr) Meiosis Fertilization Gametes All F1 plants produce yellow-round seeds (YyRr) F1 Generation Meiosis LAW OF SEGREGATION LAW OF INDEPENDENT ASSORTMENT Two equally probable arrangements of chromosomes at metaphase I Anaphase I Metaphase II Gametes F2 Generation Fertilization among the F1 plants

Morgan’s Experimental Evidence: Scientific Inquiry ● The first solid evidence associating a specific gene with a a specific chromosome came from Thomas Hunt Morgan, an embryologist

Morgan’s Choice of Experimental Organism: Fruit Flies! ● Characteristics that make fruit flies a convenient organism for genetic studies: -They breed at a high rate -A generation can be bred every two weeks -They have only four pairs of chromosomes

● Morgan noted WILD TYPE, or normal, phenotypes that were common in the fly populations ● Traits alternative to the wild type are called mutant phenotypes

Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair ● In one experiment, Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type) -The F1 generation all had red eyes -The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes ● Morgan determined that the white-eye mutant allele must be located on the X chromosome ● Morgan’s finding supported the chromosome theory of inheritance!

P Generation F1 Generation F2 Generation P Generation Ova (eggs) Sperm F1 Generation Ova (eggs) Sperm F2 Generation

Linkage & Gene Maps

The Big Question… ● It may be easy to see that genes located on DIFFERENT chromosomes assort independently but what about genes located on the SAME chromosome?

Thomas Morgan’s Research ● Morgan identified more than 50 genes on Drosophila’s 4 chromosomes. ● He discovered that many seemed to be “linked” together They are almost always inherited together & only rarely become separated ● Grouped genes into 4 linkage groups

Hmmm... 4 chromosomes & 4 linkage groups

Morgan’s Conclusion: ● Each chromosome is actually a group of linked genes ● BUT Mendel’s principle of independent assortment still holds true ● It is the chromosomes that assort independently!! Mendel missed this because 6 of the 7 traits he studied were on different chromosomes.

So… ● If 2 genes are found on the same chromosome are they linked forever? NO!! ● CROSSING OVER during Meiosis can separate linked genes

Parental-type offspring Recombinant offspring Testcross parents Gray body, normal wings (F1 dihybrid) Black body, vestigial wings (double mutant) Replication of chromosomes Replication of chromosomes Meiosis I: Crossing over between b and vg loci produces new allele combinations. Meiosis I and II: No new allele combinations are produced. Meiosis II: Separation of chromatids produces recombinant gametes with the new allele combinations. Recombinant chromosomes Ova Sperm Gametes Ova Testcross offspring 965 Wild type (gray-normal) 944 Black- vestigial 206 Gray- vestigial 185 Black- normal Sperm Recombination frequency = 391 recombinants  100 = 17% 2,300 total offspring Parental-type offspring Recombinant offspring

Gene Maps ● Alfred Sturtevant was a graduate student working in Morgan’s lab part-time in 1911 ● He hypothesized that the farther apart 2 genes are on a chromosome the more likely they are to be separated by crossing-over ● The rate of at which linked genes are separated can be used to produce a “map” of distances between genes Alfred Sturtevant 1891-1970

Gene Maps ● This map shows the relative locations of each known gene on a chromosome

Linkage Maps ● A linkage map is a genetic map of a chromosome based on recombination frequencies ● Distances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequency ● Map units indicate relative distance and order, not precise locations of genes

Recombination frequencies 9% 9.5% 17% b cn vg Chromosome

I IV II Y X III Mutant phenotypes Short aristae Black body Cinnabar eyes Vestigial wings Brown eyes 48.5 57.5 67.0 104.5 Long aristae (appendages on head) Gray body Red eyes Normal wings Red eyes Wild-type phenotypes

Sex-linked genes exhibit unique patterns of inheritance ● In humans and other animals, there is a chromosomal basis of sex determination

XX XY ● Human somatic cells contain 23 pairs of chromosomes -22 pairs of autosomes (same in males & females) -1 pair of sex chromosomes (XX or XY) -Females have 2 matching sex chromosomes: XX -Males are XY XX XY

Inheritance of Sex-Linked Genes ● The sex chromosomes have genes for many characters unrelated to sex ● A gene located on either sex chromosome is called a SEX-LINKED gene ● Sex-linked genes follow specific patterns of inheritance

Sperm Sperm Sperm Ova Ova Ova

● Some disorders caused by recessive alleles on the X chromosome in humans: -Color blindness -Duchenne muscular dystrophy -Hemophilia

● When a gene is located on the X chromosome, females receive 2 copies of the gene, and males receive only 1 copy Example: Color-blindness (c) is recessive to normal vision (C), and it is located on the X chromosome; hemophilia

XC Xc Xc Y EXAMPLE PROBLEM: ● A female heterozygous for normal vision: (we say she has normal vision, but is a carrier of the colorblindness allele) ● A male who is colorblind: XC Xc Xc Y

What is the probability that: a) they will have a son who is colorblind?   b) they will have a daughter who is colorblind? c) their first son will be colorblind? d) their first daughter will be carrier? XC Xc 1/4 (25%) 1/2 (50%) Xc Y XC Xc Xc Xc XC Y Xc Y

XH Y XH Xh EXAMPLE PROBLEM: x ● Hemophilia is a hereditary disease in which the blood clotting process if defective. Classic hemophilia results from an abnormal or missing clotting factor VIII; it is inherited as an X-linked recessive disorder (h). ● If a man without hemophilia and a woman who is a carrier of the hemophilia allele have children, what is the probability that… XH Y XH Xh x

what is the probability that: a) they will have a daughter with hemophilia?   b) they will have a son with hemophilia? c) their first son will have hemophilia? d) their first daughter will be a carrier? XH Xh 0/4 (0%) 1/4 (25%) 1/2 (50%) XH Y XH XH XH Xh XH Y Xh Y

Pedigree Charts

Queen Victoria’s Legacy in Royal Families of Europe

X-inactivation in Female Mammals ● In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development ● If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character

Two cell populations in adult cat: Active X Early embryo: Orange fur X chromosomes Cell division and X chromosome inactivation Inactive X Inactive X Black fur Allele for orange fur Allele for black fur Active X

Tortoise-shell cats! (a.k.a. “Torties”) XBXb

So, what about the Y chromosome?

Alterations of chromosome number or structure cause some genetic disorders ● Large-scale chromosomal alterations often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders

Abnormal Chromosome Number ● In NONDISJUNCTION, pairs of homologous chromosomes do not separate normally during meiosis ● As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy

Meiosis I Nondisjunction Meiosis II Nondisjunction Gametes n + 1 n + 1 n – 1 n – 1 n + 1 n – 1 n n Number of chromosomes Nondisjunction of homologous chromosomes in meiosis I Nondisjunction of sister chromatids in meiosis I

● Aneuploidy results from the fertilization of gametes in which nondisjunction occurred ● Offspring with this condition have an abnormal number of a particular chromosome

in which an organism has more than two complete sets of chromosomes ● a TRISOMIC zygote has three copies of a particular chromosome ● a MONOSOMIC zygote has only one copy of a particular chromosome ● Polyploidy is a condition in which an organism has more than two complete sets of chromosomes

Alterations of Chromosome Structure ● Breakage of a chromosome can lead to four types of changes in chromosome structure: -Deletion removes a chromosomal segment -Duplication repeats a segment -Inversion reverses a segment within a chromosome -Translocation moves a segment from one chromosome to another

Deletion A deletion removes a chromosomal segment. Duplication A duplication repeats a segment. Inversion An inversion reverses a segment within a chromosome. A translocation moves a segment from one chromosome to another, nonhomologous one. Reciprocal translocation

Human Disorders Due to Chromosomal Alterations ● Alterations of chromosome number and structure are associated with some serious disorders ● Some types of aneuploidy appear to upset the genetic balance less than others, resulting in individuals surviving to birth and beyond ● These surviving individuals have a set of symptoms, or syndrome, characteristic of the type of aneuploidy

Down Syndrome: ● Down Syndrome is an aneuploid condition that results from three copies of chromosome 21 ● It affects about one out of every 700 children born in the United States ● The frequency of Down Syndrome increases with the age of the mother

Aneuploidy of Sex Chromosomes ● Nondisjunction of sex chromosomes produces a variety of aneuploid conditions ● Klinefelter syndrome is the result of an extra chromosome in a male, producing XXY individuals ● Monosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable monosomy in humans

Disorders Caused by Structurally Altered Chromosomes: ● One syndrome, cri du chat (“cry of the cat”), results from a specific deletion in chromosome 5 ● A child born with this syndrome is mentally retarded and has a catlike cry; individuals usually die in infancy or early childhood ● Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes

Translocated chromosome 9 Normal chromosome 9 Reciprocal translocation Translocated chromosome 9 Philadelphia chromosome Normal chromosome 22 Translocated chromosome 22