Human Genetics

1
Human Genetics

• Chapter 14

2
Quick Chromosome Review

• What are chromosomes made of?
• DNA PROTEINS
• When are chromosomes visible?
• CELL DIVISION
• What does it mean to be diploid?
• Have two sets of chromosomes
• One from mom one from dad!
• Which cells are not diploid? Why?
• Gametes haploid sperm (23) haploid egg (23)
• They must combine to form a diploid
• zygote (46)!

3
Sex Chromosomes

• Determine an individuals gender
• Two chromosomes within the genome
• XX Female
• All human eggs carry an X chromosome (23, X)
• X chromosome has gt 1200 genes
• XY Male
• About half of sperm cells carry an X, the other
  half carry a Y (23, X or 23, Y)
• Y chromosome is much smaller and has only about
  140 genes
• mostly associated with male sex
• determination and sperm development

4
Autosomal Chromosomes

• Remaining 44 human chromosomes
• Humans have 46 total chromosomes
• 44 autosomal chromosomes (22 pairs)
• 2 sex chromosomes
• To correctly label a karyotype or summarize the
  number of chromosomes in a human cell
• 46, XX (females) 46, XY (males)

5
Human Pedigrees

• Chart that shows relationships within a family
• Shows presence or absence of a trait and how it
  is passed on through a family
• used for any species
• used to infer genotypes of family members
• can determine if allele is dominant,
• recessive, autosomal, or sex-linked
• used to determine who in a family is
• at risk for genetic conditions by
• genetic researchers or counselors

6
Human Pedigree
Children are placed from oldest ? youngest
Key explains what trait is!
7
Ff

• Steps
• Identify all people who have the trait.
• For the purpose of this class all traits will be
  given to you. In other instances, you would have
  to determine whether or not the trait is
  autosomal dominant, autosomal recessive, or
  sex-linked.
• In this example, all those who have the trait
  are homozygous recessive.
• Can you correctly identify all genotypes of this
  family?
• F- Normal
• f- cystic fibrosis

Key affected male affected
female unaffected male
unaffected female
8
Pp
Pp

• PKU
• P- Unaffected
• p- phenylketonuria

pp
Pp
pp
PP or Pp
pp
Pp
Pp
9

• H-huntingtons disease
• h-Unaffected

Hh
hh
Hh
hh
Hh
hh
hh
Hh
hh
10
Sex-Linked Inheritance

• Colorblindness

XCY
XcXc
XcY
XCXc
XcY
XCXc
XcY
11
Karyotypes

• To look at the human genome, biologists
  photograph human chromosomes during mitosis
  (usually metaphase)
• Cut them out and arrange them into a picture
  called a karyotype
• Shows the complete diploid set of chromosomes
  grouped together
• in pairs
• Arranged in order of decreasing
• size

12
Normal Human Male (46, XY)
13
Normal Human Female (46, XX)
14
X Chromosome Inactivation

• Females have an extra X chromosome
• Most of genes in one of X chromosomes turned off
• Forms dense region in nucleus called a Barr body
• Same process in other mammals
• i.e. calico cats

15
Human Genetic Disorders

• Review what is a mutation?
• Change in DNA sequence
• Changes proteins by altering amino acid sequence!
• Can directly affect the phenotype expressed!
• Many genetic disorders are caused
• by changes in an individual gene!

16
Sickle Cell Disease

• Caused by a defective allele for a protein in
  hemoglobin
• Causes hemoglobin molecules to stick together and
  form sickle shape
• More rigid and get stuck in capillaries
• Results in loss of blood flow and damage to
  cells, tissues, and organs

17
Cystic Fibrosis

• Known as CF
• Results from deletion of just three bases in gene
  for a protein called CFTR
• Protein is destroyed and doesnt work as a
  transport protein, so proper ions arent
  transported across cell membrane
• Recessive trait need two copies of defective
  allele for CF
• Serious digestive problems and
• thick, heavy mucus clogs lungs and
• breathing passageways

18
Huntingtons Disease

• Caused by dominant allele for a protein found in
  brain cells
• Mental deterioration, uncontrollable movements,
  appears in middle age

Dominant, Autosomal
19
Genetic Advantages

• How do fatal alleles remain in the gene pool?
• Heterozygous individuals often show genetic
  advantages in certain situations
• Those heterozygous for sickle-cell are highly
  resistant to malaria
• Those heterozygous for CF had an advantage in
  medieval times and
• were resistant to Typhoid Fever

20
Chromosomal Disorders

• Errors can occur in meiosis
• Homologous chromosomes can fail to separate
  during Anaphase I
• Nondisjunction
• Results in gametes with an abnormal number of
  chromosomes
• Trisomy 3 copies of a chromosome
• Down syndrome Trisomy 21
• Mild to severe mental retardation
• High frequency of birth defects

21
Male 47, XY, 21Female 47, XX, 21
Trisomy 21
22
Sex Chromosome Disorders

• Turners Syndrome
• Nondisjunction of X chromosome
• Female inherits only one X chromosome
• Results in sterility and reproductive organs do
  not develop properly
• Klinefelters syndrome
• Males inherit extra X chromosome
• Interferes with meiosis and
• usually causes sterility
• No cases of babies born without X!
• Necessary for survival of embryo

XXY
23
Human Genome Project

• Launched in 1990
• Main goal sequence 3 billion base pairs of human
  DNA and identify all human genes
• Completed in 2003
• Completed genomes of many other organisms while
  working through human genome
• 40 of our proteins have strong similarity to
  proteins in many of those organisms (fruit fly,
  worms, yeast)

24
Human Genome Project

• Only about 2 of genome encodes instructions for
  synthesis of proteins
• Large areas of chromosomes with very few genes
• Pinpointed genes and associated particular
  sequences in those genes with diseases and
  disorders
• Identified about three million locations where
  single-base DNA differences occur in humans
• Help us find sequences associated with diabetes,
  cancer, and other health problems

25
HGP What now?

• Ethical, legal, social issues
• Who owns and controls genetic information?
• How does genetic privacy relate to medical
  privacy?
• May 2008 Genetic Information Nondiscrimination
  Act
• Prohibits US insurance companies and employers
  from discriminating on basis of information
  derived from genetic tests
• Still dont understand as many as 50 of the
  human genes thus far discovered