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Sex Chromosomes and Nondisjunction Diseases. A. P. Biology Chapter 15 Mr. Knowles Liberty Senior High School. Human Chromosomes. 46 Total (23 pair) 22 pair are perfectly matched- autosomes . Remaining pair- sex chromosomes . Human: XX normal female XY normal male
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Sex Chromosomes and Nondisjunction Diseases A. P. Biology Chapter 15 Mr. Knowles Liberty Senior High School
Human Chromosomes • 46 Total (23 pair) • 22 pair are perfectly matched-autosomes. • Remaining pair- sex chromosomes. • Human: XX normal female XY normal male • Y chromosome highly condensed with a few dozen genes.
Chromosomal Basis of Sex • Two similar X’s = human female • Two dissimilar X and Y = human male • NOT true for all diploid organisms. • Both sex chromosomes behave like homologues during meiosis in the testes and ovary. They may cross-over at Pro I. • Each gamete receives one sex chromo.
Spermatogenesis Oogenesis 44 + XY 44 + XX 22 + X 22 + X 22 + X 22 + Y
Chromosomal Basis of Sex • Each ovum contains one X chromosome. • Sperm have either X OR the Y chromosome.
What determines sex in humans? • Before two months, all fetuses are anatomically the same. • The gonads are generic and can become either ovaries or testes. • Depends upon hormone levels in the embryo. • Trigger is the SRY gene on the Y.
The Human Y Chromosome • Encodes a protein called SRY- the “sex-determining region of Y”. SRY is a regulator for other genes on other chromosomes. • Responsible for development of testes. • Without SRY, the gonads develop into ovaries. Female is default sex in humans.
Sex-linked Genes Have a Unique Pattern of Inheritance • In 1910, Thomas Hunt Morgan saw a remarkable mutation in Drosophila. • Saw a mutant male with white eyes! • Followed Mendel’s techniques- F1 showed that the white phenotype was recessive to wild-type red eye color. • F2 - 3:1 red : white but all white eyes were MALE!
Explanation to Morgan’s Dilemma • The gene that causes the white eye phenotype is on the X chromosome and not found on the Y. • Proved that inheritable traits do reside on the chromosomes. • Any trait or gene found on the X chromosome- sex linked.
Mapping the First Chromosome • In 1913, A. H. Sturtevant located the relative positions of 5 recessive genes on the X chromosome of Drosophila by estimating their frequency of recombination due to X-over. • This was a linkage map.
Genetic Maps • Cross-over occurs more frequently between two genes farther apart. • Use x-over rates in progeny to plot relative position of genes on chromosomes- Linkage Map. Distance is measured in frequency of recombination between two genes. • Genes very close are linked- they do not x-over.
Genetic Map • A linear sequence of genetic loci on a particular chromosome. Linkage Maps are based on frequency of recombination between two loci. • What about genes very far apart? • Linkage maps are NOT a picture of chromosomes. NOT physical map of genes.
Cytological Maps of Chromosomes • Locate genes with respect to chromosomal features such as banding patterns. • G-banding (Giemsa staining) stains • C-banding (Centromere staining) stains heterochomatin of the centromere.
Human Genome Project • Physical sequencing of the DNA on each chromosome. • Shows the distance between loci in DNA nucleotides. • Finished Human Genome Project in Spring 2000. Identified 30,000 genes in humans in Winter 2001. • Other genomes sequenced: C. elegans, D. melongaster, many prokaryotes.
X -linked Traits • If a sex-linked trait is recessive, female will be heterozygous; one X comes from the mother and the other X from the father. Seldom will be homozygous for the genes on the X chromosome. • Males only inherit X from the mother- called hemizygous. More likely to be affected by X-linked diseases.
>60 X-linked Human Diseases • Colorblindness • Duchenne and Becker Muscular Dystrophies • Albinism-Deafness Syndrome • Two proteins (Factor 8 and 9) for blood clotting. Mutations here cause Hemophilia, Hemophilia A and B. • SCID (Boy in the Bubble, Johnny T.)
SCID • David Vetter- lacked cytokines for the immune system. • Died at age 12.
Duchenne’s Muscular Dystrophy • On the X chromosome, the gene for dystrophin- a protein found attached to the inner surface of the sarcolemma in normal muscle fibers (cells). • Dystrophin regulates Ca+ ion channels- mutations keep the channels open too long. • Candidate for gene therapy-successful in rats.
Female Mammals are like Floor Tile! • Males and females have the same amount of proteins encoded by the X-linked genes! HOW? • One X chromosome in each female cell becomes inactive during embryonic development- X -inactivation. • Males = Female X-linked gene activity.
X - Inactivation • The inactive X chromo. Becomes condensed and attaches to the inside of the nuclear envelope- Barr Body. • Most genes are NOT expressed. • Barr Body Chromosomes are reactivated in ovary cells--> ova.
X - Inactivation • Mary Lyon - showed that the selection of which X will become the Barr body is random and independent in each embryonic cell present at the time of X-inactivation. • After the X is inactive in a particular cell, all the mitotic descendents of that cell have the same X inactivated.
Females are Protein Mosaics! • Mosaics- half of her cells have the active X derived from the mother, half of her cells have the active X from the father. • If heterozygous, the same tissue will express one allele from one X chromosome and another allele from the other X chromosome
What would a carrier with X-linked disease look like? Diseased Phenotype? Normal?
Mechanism of X-Inactivation • Attachment of CH3 groups to cytosines. • A gene is active only on the Barr body chromosome-XIST (X-inactive specific transcript)- encodes an RNA. These RNA molecules bind to the chromosome from which they were made. • But which X will have an active XIST gene? Unknown!
Alteration of Chromosome Numbers • Primary Nondisjunction- members of a pair of homologous chromosomes do not move apart properly during anaphase of meiosis I. • Unequal distribution of chromosomes in the daughter gametes.
Nondisjunction Leads to Abnormal Chromo. # in Zygote • If the aberrant gamete units with a normal gamete, the offspring will have an abnormal # of chromosomes- aneuploid. • Aneuploid: 2n + 1 = Trisomy 2n - 1 = Monosomy
Monosomics • Organisms which have lost one copy of a chromosome. • Do Not Survive Development! • Lethal Error!
Trisomics • Most do not survive either. • Some trisomies do survive for a time: Trisomy 13, 15, 18-severe developmental defects, die within a few months. Trisomy 21- Down Syndrome. Trisomy 22- mentally retarded.
