The Human Genome

From Peas and fruit flies to humans…

What is a genome???

• All the genetic information (genes) that make up an organism

What makes us human?• Analyze human chromosome…

• Karotype– Picture of all the chromosomes

in an organism

– Autosomes• CHROMOSOMES 1-44 (pairs 1-22)

• Autosomal chromsomes

– Sex chromosomes• Determine a person’s sex (male XY

or female XX)

• Chromosome 45 and 46 (set 23)

Pedigree Charts• Shows relationships within a family

• Genetic counselors use these to infer the genotypes of family members

• Look at each generation different symbols used

Disorders can be recessive or dominant

Recessive disorders

• Disorder phenylketonuria (PKU)• Caused by an autosomal recessive allele on

chromosome 12• People with this disorder lack the enzyme to

break down phenylalanine (amino acid found in milk and many other foods)– In newborns, this causes a build up of phenylalanine

in tissues during the first few years of life and lead to mental retardation

– Newborns are commonly tested for PKU and then put on a low phenylalanine diet if they have the disorder

Autosomal Recessive Allele• Tay-Sachs Disease

– Recessive allele in Jewish families of central and eastern Europe ancestry

– Lack the enzyme to break down lipids in neural cells

• Lipid accumulation in brain cells

– Leads to nervous system break-down and death in the first few years of life

Autosomal Recessive Disorders

• Cystic Fibrosis

– Do not have the gene that regulates mucus production

– Excess mucus in lungs, digestive tract, and liver

– Increased susceptibility to disorders

– Lung transplants usually needed after childhood

Autosomal Dominant Disorders

• You will express disorder if you are homozygous or heterozygous dominant for that trait– You also have higher chances

of passing onto your children

• Dwarfism (achondroplasia)

• Huntington’s Disease– Nervous system disorder

Co-Dominant Alleles Disorders

• Sickle cell anemia• 1/500 African Americans have the

disorder• Co-dominant allele• Causes blockages in blood vessels,

preventing oxygen from getting to other cells and tissues

• Beneficial in central and east Africa because it helped destroy malaria– If you had SCA, your body would

destroy the sickle cells to protect itself and in the process, destroy the malaria parasite as well

Sex-Linked Disorders

• Many sex-linked genes are found on x-chromosome

• Many genetic disorders are sex-linked

• Males have just ONE x chromosome, so whatever the X chromosome is carrying (dominant or recessive) will be expressed

• Fathers can pass it to their daughters and the disorder can show up in the daughters sons

Sex-linked Disorders• Red-green Color-blindness

– 1/10 men– 1/100 women

• Hemophilia– Two important genes on x-chr control

blood clotting– Person with disorder can die from minor

cuts – Recessive allele in either gene can cause it

• Duchenne Muscular Dystrophy– Caused by defective version of a gene for a

muscle protein– Progressive weakening and loss of skeletal

muscle1/3000 males

X-chromosome Inactivation• Females have XX and males have XY…is

the second X chr in females needed??• British Geneticist Mary Lyon • In female cells, one x-chromosome is

randomly shut off…this “shut off” chromosome is called a Barr Body

• Different X-chrm are switched off in different cells

• Generally not found in males b/c X-chrmneeds to be ACTIVE

• Occurs in other mammals as well

• Barr bodies in cats

• Gene that controls color of coat spots is located on the X-chrm

– In a female, one X-chrm may have the allele for orange spots and the other X-chrm may have the allele for black spots

– Different cells in different parts of the cat’s body are switched off= different colored spots on different parts of the cat…mix or orange and black spots

– Males only have ONE active X-chrm…therefore, will they have different colored spots?

• No…only psots of ONE color (b/c on ONE active X)

• This is one way to determine the sex of a cat…cat with black AND orange spots is almost always certainly female

Chromosomal Disorders

• Mechanics of meiosis (where we separate chromosomes) is usually pretty good

• But nobody’s perfect…mistakes happen….

• Most common problem…– Nondisjunction: when homologous chromosomes fail

to separate properly

– Literally means “not coming apart”

– If this occurs, ABNORMAL #s of chromosomes may find their way into gametes and a disorder of chromosome number may result

Nondisjunction

• If one of the gametes with an ABNORMAL # ends up getting fertilized, MAJOR problems!!!– Trisomy: “three bodies”

• Occurs when an autosomal chromosome fails to separate during meiosis

– When do chrm separate?

» Anaphase I and Anaphase 2

• One gamete ends up with an extra copy of a chromosome and then the fertilized zygote ends up with 3 copies of a chrm instead of 2

• Example: Downs Syndrome

Down Syndrome• Extra copy of chromosome 21

– 1/800 baby’s are born with this disorder

• Produces mild to severe retardation

• Increased susceptibility to diseases, slower development, and higher frequency of birth defects

• How can one little extra copy cause so many problems?– Scientists are still trying to figure that

out…now that they have used gene mapping and identified all the genes on chromosome 21, they can begin experimenting on this problem

Sex Chromosome Disorders• What happens if nondisjunction happens to the sex

chromosomes???• We know we need at least one X chromosome….

– No embryos have been found with just a Y chromosome so we now X chrm contains vital genes!

• Turners Syndrome– Females receive only one X chromosome– Karotype 45, X– Unable to reproduce, sex organs do not develop at puberty

• Klinefelters Syndrome– Males receive an extra X chromosome– Karotype 47, XXY– Prevents individuals from reproducing– Cases of individuals with XXXY and XXXXY– Y chromosome contains “sex determining region” SDR, which gives

male characteristics and development– If region is absent, embryo develops into female

Turner’s Syndrome

• What about an extra Y?

• Males with 47, XYY produce more male hormones and express a more expressive behavior– More testosterone=more

aggressive behavior

• Higher number of men in prison for violent crimes have XYY however there is a large population of men with XYY that do not exhibit (or at least act upon) this aggression– Cannot use this as an excuse for

aggressive behavior or else criminals would be pleading an extra Y instead of insanity :-o