Human Genetics

Human Chromosomes• 23 Pairs - 22 Autosomes - 1 Sex

chromosome• 1 set contributed

by mother• 1 set contributed

by father

Chromosomal disorders• How many chromosomes does a

normal human gamete have?• What happens if a gamete fails to

separate chromosomes properly? - Nondisjunction – results in…. - Aneuploidy – any difference from

the normal 46 chromosomes

When does nondisjunction happen?

How do you diagnose nondisjunction? Karyotyping• Picture of the

chromosomes• Sample collected

by Amniocentesis in at risk mothers

- mothers over 35 - families with

histories of genetic disorders

Normal Karyotypes

46, XX 46, XY

Nondisjunction disorders• Down Syndrome - Extra copy of the 21st Chromosome - 47, X_, +21 - 1/700 live births in the US• Characteristics - characteristic facial features, short stature;

heart defects - susceptibility to respiratory disease, shorter

lifespan - prone to developing early Alzheimer's and

leukemia - often sexually underdeveloped and sterile,

usually some degree of mental retardation. - Down Syndrome is correlated with age of

mother but can also be the result of nondisjunction of the father's chromosome 21.

Nondisjuncton in sex chromosomes• Turner’s Syndrome (Monosomy X) - 45, X - 1/5000 live births• Characteristics - short stature - characteristic “webbed” neck - infertile - normal mental development

• Klinefelter’s Syndrome - 47, XXY• Characteristics - Male sex characteristics - Underdeveloped testes - Sterile - Some female secondary sex

characteristics (breast and hip growth)

Can you tell what is going on in this karyotype?

Can you tell what is going on in this karyotype?

Patau Syndrome• Trisomy 13 - Severe mental and physical

problems - Cleft lip, palate, small head, heart

problems, small limbs

What is wrong here and what would be the notation?

Edwards Syndrome• Trisomy 18 - Severe mental and physical

disabilities - Rarely live past one year

What is wrong here?

Other Chromosomal Disorders• Translocations : Philadelphia

Translocation t(9;22)(q34;q11.2)

• Deletions : Fragile X, Cri du Chat

• Duplications : Rare

Cri du Chat Syndrome• High pitch cry (cat

like)• Downward eye

slant• Mental retardation• Partially webbed

fingers or toes• Small head and

eyes

Following Traits : Pedigrees• Chart showing relationships and

tracing a particular trait through a family

Autosomal Dominant• Appears in every generation• An afflicted child must have an

afflicted parent

Example: Huntington’s Disease• Autosomal dominant

CAG repeat• Degeneration of

nerves• Person begins life

normally• Nerves degenerate

over time• Jerky motion, slurred

speech, mental retardation

Other Dominant Diseases• Achondroplasia – Dwarfism• Hypercholesterolemia – high

cholesterol• Osteogenesis imperfecta – brittle

bones• Polydactyly – 6 fingers and toes• Many others

Recessive Disorders• Appears intermittently through

generations (up to 25% of individuals)

• No sex preference• Afflicted child does not necessarily

have an afflicted parent

Example : Albinism• Lack of pigment in

skin, hair and eyes• No common

negative health problems besides increased risk of skin cancer

• Defective gene for the production of melanin

Example: Cystic Fibrosis

• Thick, sticky mucous

• Effects all secretory organs

• CFTR protein has a single AA change

Other Recessive Disorders• Phenylketonuria – accumulation of

phenylalanine in tissues• Tay-Sachs disease – lipid

accumulation in brain cells• Galactosemia – inability to

metabolize galactose• Many others

Codominant disorder: Sickle cell anemia• NN = normal

hemoglobin Nn = sickle cell

trait nn = sickle cell

anemia• Evolution: Library:

A Mutation Story

Sex-Linked Inheritance• Trait only (usually)

expressed in males• Skips generations

in families

Hemophilia in the Royal Family

Other sex-linked recessive disorders• Duchene muscular dystrophy• Red-green colorblindness• Fragile-X syndrome

Imprinting and DisordersPrader Willi Syndrome Angelman Syndrome

Blue people of Troublesome Creek