1. Chromosomes and Human Genetics

2. The Chromosomal Basis of Inheritance A time to review A gene – a unit of information about a heritable trait – found at a specific location on a chromosome Cells with a diploid chromosome number have pairs of homologous chromosomes All but one pair (the sex chromosomes) are normally the same length Genes mutate which means a pair of genes on homologous chromosomes may or may not be the same The slightly different forms of a gene that occur among individuals of a population are called alleles

3. The Chromosomal Basis of Inheritance Mutations The most common form of an allele is called the wild-type allele and the less common form is called the mutant allele All genes on the same chromosome are physically connected The farther apart any two genes are along the length of the chromosome, the more vulnerable they are to crossing over This crossing over is a part of genetic recombination that introduces novel combinations of alleles in chromosomes If chromosomal structure or the parental number changes in mitosis or meiosis then these chromosomal abnormalities can have severe phenotypic consequences

4. Autosomes and Sex Chromosomes Autosomes have pairs of homologous chromosomes A unique chromosome occurs in either females or males of many species, but not both Human female is XX Human male ix XY This XY form is common among mammals, fruit flies, and many other animals In butterflies, moths, birds, and certain fishes the sex chromosomes are identical in males and not identical in females

5. Autosomes and Sex Chromosomes Human X and Y Chromosomes Y is a lot shorter – almost like it is a remnant of the X The X and Y differ in the genes they carry They do act as homologues during meiosis They determine the gender of the human Normal female eggs have one X chromosome Half the sperm carry an X chromosome and half carry a Y chromosome XX = female XY = male

6. Autosomes and Sex Chromosomes The SRY gene is one of 330 on the human Y chromosome and is the master gene for male sex determination Triggers the formation of testes which makes testosterone which governs the emergence of the male sexual traits A female embryo has no SRY gene The absence of SRY triggers the formation of ovaries which make estrogen which governs the development of the female sexual traits The human X chromosome carries 2,062 genes Distribution of body fat and hair Most genes deal with nonsexual traits – which can be expressed in both males and females Blood-clotting functions for example – hemophilia is an X- linked genetic disorder

7. Karyotyping A karyotype is a preparation of an individual’s metaphase chromosomes sorted out by their defining visual features Abnormalities can be detected by comparing to a standard karyotype How do we get these Sample cells in a solution that stimulates growth Add chemical cholchicine to arrest cells at metaphase (blocks spindle formation) Cells centrifuged and put in a hypotonic solution to split them open Mount on slides, fix and stain

8. Karyotyping

9. Impact of Crossing Over on Inheritance All of the genes at different locations along the length of a chromosome belong to the same linkage group. They do not all assort independently at meiosis Crossing over between homologous chromosomes disrupts gene linkages and results in nonparental combinations of alleles in chromosomes The farther apart two genes are on a chromosome, the greater will be the frequency of crossing over and genetic recombination between them

10. Human Genetic Analysis We live under variable conditions and in diverse environments We select our own mates We reproduce if and when we want to (assuming that both couples are fertile) Study several generations to get an idea as to what is going on genetically Called a pedigree analysis

11. Pedigree Analysis for Polydactyly Polydactyly is a dominant trait – pentadactyly is a recessive trait

12. Human Genetic Analysis Genetic abnormality A rare or uncommon version of a trait Usually not life-threatening Genetic disorder Heritable condition that sooner or later gives rise to mild or severe medical problems A set of symptoms or syndrome characterizes each abnormality or disorder Disease is an illness that results from an infection, dietary problems, or environmental factors, NOT from a heritable mutation We will call them genetic diseases

13. Examples of Human Inheritance Patterns Autosomal Dominant Inheritance Achondroplasia Mini Me?!?!

14. Examples of Human Inheritance Patterns Autosomal Dominant Huntington’s Disease – nervous system deteriorates, involuntary muscle action

15. Examples of Human Inheritance Patterns Autosomal Recessive Inheritance Galactosemia No enzyme to break down lactose Causes malnutrition, diarrhea, vomiting, damage to eyes, liver, and brain If untreated they die early Restrict dairy products

16. Examples of Human Inheritance Patterns X-linked Inheritance Found only on the X chromosome Females are not affected as often as males A son can’t inherit an x-linked allele from his father, but a daughter can – WHY? When she does each of her sons has a 50% change of inheriting it Color blindness Red-Green – person sees fewer than 5 colors (normally 150)

17. Examples of Human Inheritance Patterns X-linked inheritance Hemophilia A blood clotting disorder Clotting proteins are products of genes on the X- chromosome About 1 in 7000 males is affected

18. Too Young, Too Old Hutchinson-Gilford progeria syndrome Affects one in 8 million Accelerated aging Likely arises from a spontaneous mutation No evidence it runs in families Most die in their early teens from strokes or heart attacks Oldest living was 18

19. They are not yet 10 years old

20. Altered Chromosomes Chromosome structure can change spontaneously or by exposure to chemicals or irradiations Some can be detected Some have severe or lethal outcomes Duplication – gene sequences that are repeated several to many thousands of times No information lost Some cause a variety of neural problems and physical abnormalities Some may be useful

22. Altered Chromosomes Inversions Part of a sequence of DNA within the chromosome becomes oriented in the reverse direction with no molecular loss Not a problem it if does not interrupt a crucial gene region If it mispairs during meiosis it can lead to chromosome deletions in gametes May not know it until you have kids

24. Altered Chromosomes Deletion A loss of a portion of a chromosome In mammals, most deletions cause serious disorders or are lethal Disrupts growth, development, and maintenance activities Cri-du-chat Single deletion in chromosome 5 Abnormally shaped larynx and mental impairment When they cry they sound likes cats

26. Altered Chromosomes Translocation A broken part of a chromosome attached to a different chromosome Usually both chromosomes exchange broken parts May not pose a threat if the instructions don’t get garbled May cause sarcomas, lymphomas, myelomas, and leukemia Philadelphia Chromosome - lethal

29. Changes in Chromosome Number Aneuploidy – extra chromosomes Autosomal aneuploidy is usually fatal for humans and is linked to most miscarriages Polyploidy Cells have 3 or more of each type of chromosome Many plants Strawberries Usually results from nondisjunction – one or more pairs of chromosomes don’t separate as they should during mitosis or meiosis

30. Trisomy 21 or Down Syndrome

31. Changes in Sex Chromosome Number Females Turner Syndrome – only 1 X chromosome XXX syndrome Males Kleinfelter Syndrome – XXY XYY (criminals)

32. Prospects in Human Genetics Bioethical Questions Abortion Genetic Screening – Amniocentesis

33. Prospects in Human Genetics Genetic Counseling Preimplantation Diagnosis In vitro fertilization (Test Tube Babies)