Chromosomes and Human Genetics

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

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

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

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

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

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

Karyotyping

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

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

Pedigree Analysis for Polydactyly

Polydactyly is a dominant trait – pentadactyly is a recessive trait

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

Examples of Human Inheritance Patterns

• Autosomal Dominant Inheritance• Achondroplasia

Mini Me?!?!

Examples of Human Inheritance Patterns

• Autosomal Dominant• Huntington’s Disease – nervous system deteriorates,

involuntary muscle action

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

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)

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

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

They are not yet 10 years old

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

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

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

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

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

Trisomy 21 or Down Syndrome

Changes in Sex Chromosome Number

• Females• Turner Syndrome – only 1 X chromosome• XXX syndrome

• Males• Kleinfelter Syndrome – XXY• XYY (criminals)

Prospects in Human Genetics

• Bioethical Questions• Abortion• Genetic Screening – Amniocentesis

Prospects in Human Genetics

• Genetic Counseling• Preimplantation Diagnosis

• In vitro fertilization (Test Tube Babies)