Download CHAPTER 14 THE HUMAN GENOME

14-1
Human Heredity
A. Human chromosomes
- chromosomes are analyzed by taking a photograph of
condensed chromosomes during mitosis
- the chromosomes are then cut out of the photograph and
grouped together in pairs
- a picture of chromosomes arranged this way is known
as a karyotype (See Fig 14-2 pg. 341)
Normal human karyotype
- normal karyotypes show 46 chromosomes which are
labeled 1-23
- the last set (23) are the sex chromosomes which
determine the person’s sex
- the rest (1-22) are autosomal chromosomes or
autosomes
- biologists summarize the total number of
chromosomes in a human cell as 46XX (female) and 46XY
(male)
- all egg cells carry a single X chromosome (23X) and
half of all sperm carry an X (23X) or a Y (23Y)
- each chromosome contains a single, double stranded
DNA molecule
B. Human Traits
- human genes are inherited according to the same
principles discovered with Gregor Mendel’s peas
- biologists must identify an inherited trait controlled
by a single gene(not easy) by establishing that it is an
inherited trait and not the result of environmental influences
- they then study how the trait is passed from
generation to generation
- to do this, they use a chart called a pedigree which
shows the relationship in families of certain traits (See Fig
14-3)
many traits are polygenic (shapes of ears and eyes)
- many traits are strongly influenced by the environment or
nongenetic factors such as nutrition and exercise; environmental
effects are not inherited, but genes are
-
C. Human Genes
The first human genes to be identified were those that
control blood type
1. Blood Group Genes
- a number of genes are responsible for human blood
groups but the best known are the ABO blood groups and
the Rh blood groups
a. Rh- determined by a single gene with two alleles (+ and -)
- Rh+ is dominant, so those who are heterozygous
(Rh+/Rh-) are said to be Rh+ and those with 2 recessive
alleles are Rh-
b. ABO
- more complicated
- there are three alleles for this gene; IA, IB, and i
- these alleles produce antigens on the surface of the
red blood cell which are recognized by the immune system
- IA and IB are codominant; the i allele is recessive and
produces no antigen (See Fig 14-4)
2. Recessive alleles (autosomal)
- we have learned about many genes by studying genetic
disorders
- Fig 14-6 pg. 345 lists some of the more common
disorders
a. phenylketonuria (PKU)
- the enzyme needed to break down the amino acid
phenylalanine is missing
- the amino acid is found in milk, and many other foods
- if phenylalanine builds up in the tissues of a newborn, it
leads to mental retardation
- caused by an autosomal recessive allele on chromosome
12
- treated with a low phenylalanine diet
Boy with PKU who was treated reacting with
his sister (normal)
b. Tay-Sachs disease
- caused by an autosomal recessive allele
- found mostly in Jewish families of central and eastern
Europe ancestry
- results in nervous system breakdown and death
within the first few years of life
- no treatment, but there is a way to test for the allele
letting parents know if their children would be at risk for the
disorder
- fats build up in the nerve cells
- affects chromosome #15
Tay Sachs Disease
Normal and affected sibling diagnosed at 71/2
months of age
3. Autosomal dominant alleles
If you have a dominant allele for a genetic disorder, it will
be expressed
a.
achondroplasia
a form of dwarfism whereby there is a defect in the
formation of cartilage in long bones
b. Huntington’s chorea
- a nervous system disorder
- progressive loss of muscle control and mental
function until death occurs
- symptoms do not show up until around 40 years of
age when nervous system deterioration begins
4. Codominant autosomal alleles
Sickle cell disease
- sickle-shaped red blood cells causing tissue damage
D. From Gene to Molecule
In two disorders, sickle cell disease and cystic fibrosis, a small
change in a single gene affects protein structure, causing a serious
genetic disorder
1. cystic fibrosis
- a common, fatal genetic disease in people whose
ancestors were from northern Europe
- caused by a recessive allele on chromosome 7
- children develop serious digestive problems and produce
a thick mucus that clogs their lungs and breathing passageways
- only ½ of those affected survive into their 20s
- results from the deletion of 3 bases in the middle of a
sequence for a protein
- the protein allows chlorine ions to pass across
biological membranes
- the missing amino acid results in the protein folding
improperly, it cannot be transported to the cell membrane,
and it gets destroyed
- being unable to transport chlorine ions, tissues in the
body malfunction
- those with one normal allele are unaffected
2. sickle cell disease
- commonly found in African Americans
- red blood cells are bent, twisted, and more rigid than
normal red blood cells and get stuck in capillaries
- results in blood ceasing to move through blood
vessels, and cells and tissues beyond the blockage become
damaged
- produces physical weakness and damage to the brain,
heart, and spleen; can be fatal
- the gene that codes for the protein hemoglobin
(carries oxygen in the blood) differs by 1 DNA base in the
sickle cell allele causing the insertion of the amino acid
valine instead of glutamic acid
- the abnormal hemoglobin is less soluble than normal
hemoglobin
- decreases in blood oxygen levels cause hemoglobin
molecules to come out of solution and stick together
forming long chains and fibers
- there is a relationship between sickle cell in AfricanAmericans of West Central Africa and resistance to malaria
3. Dominant or Recessive?
- what makes alleles dominant, recessive, or
codominant is the nature of the gene’s protein product and
its function in the cell
- in cystic fibrosis, because only one allele supplies
enough chlorine channel proteins to function normally, it is
considered dominant recessive allele
- the sickle cell alleles are believed to be codominant
because in the heterozygous genotype, the individual
phenotype is different from someone with only normal
alleles in that they are resistant to malaria
14-2
Human Chromosomes
A. Human Genes and Chromosomes
- chromosomes 21 and 22 are the smallest human
autosomes
- they were the first two whose sequence were
determined
- their structural features are like the other human
chromosomes
- genetic disorders of chromosome #22 include an
allele that causes a form of leukemia and one associated
with neurofibromatosis ( tumor-causing disease of the
nervous system)
Neurofibromatosis
-there are also many long stretches of repetitive DNA
that do not code for protein and are unstable sites where
rearrangements can occur
- chromosome 21 is similar with one gene associated
with amyolateral sclerosis (ALS or Lou Gehrig’s disease)
- there are also regions with no genes
B. Sex-linked Genes
- there is a special pattern of inheritance for genes
located on the X and Y chromosomes
- genes located on them are said to be sex-linked
because they are formed on the chromosome that determines
sex
- more than 100 sex-linked disorders have been
mapped out on the X chromosome
- the smaller Y chromosome has only a few genes
1.
colorblindness
- the inability to distinguish certain colors
- in males, a defect in any of the 3 genes for color vision
located on the X chromosome results in colorblindness
- the most common form in red-green colorblindness
(1/10 males)
- colorblindness in females is rare (1/100)
***males have just one X chromosome, therefore, all x-linked
alleles are expressed in males even if they are recessive
***to be expressed in females, two copies of the allele must be
present, one on each chromosome
- the recessive phenotype of a sex-linked disorder is more
common in males than females
- also, men pass their X chromosome to their daughters and
the sex-linked disorder may show up in the sons of those
daughters
2. hemophilia
- another sex-linked disorder
- involves 2 genes carried on the X chromosome that
help control blood clotting
- recessive allele in either gene causes hemophilia
where a protein necessary for normal blood clotting is
missing
- hemophiliacs can bleed to death from minor cuts or
bleed internally from bumps or bruises
- treated with injections of normal clotting proteins
- 1/10,000 males are affected
Hemophilia
3. Duchenne Muscular Dystrophy
- a sex-linked disorder that results in progressive
weakening and loss of skeletal muscle
- fatal; affected individuals rarely live past early
adulthood
- affects 1/3000 males
- caused by a defective version of a gene that codes for
a muscle protein
- treatment or cure is being attempted by inserting a
normal gene into muscle cells of DMD patients
C. X Chromosome Inactivation
- females have 2 X chromosomes, but one is randomly
switched off forming a dense region in the chromosome
known as a Barr body
- Barr bodies are not found in males because with only
one X chromosome, it is still active
- Occurs in other mammals as well
Ex. fur color in female cat
D. Chromosomal Disorders
- most common disorder is when chromosomes fail to
separate during meiosis; this is called nondisjunction (See
Fig 14-15)
- this results in abnormal numbers of chromosomes in
gametes and disorders of chromosome number can occur
1. Down Syndrome
- a condition of trisomy, where two copies of an
autosomal chromosome fail to separate and an individual
may be born with 3 copies of chromosome #21
- affects 1/800 babies
- results in mild to severe mental retardation and an
increased susceptibility to many diseases and higher
incidence of birth defects
2. Sex Chromosome disorders
a. Turner’s Syndrome
- nondisjunction in females who inherit only one X
chromosome (XO)
- sterile; sex organs do not develop at puberty
Lymphedema seen in newborns with Turners
b. Klinefelter’s Syndrome
- nondisjuntion in males who inherit two X chromosomes
(XXY)
- the extra X chromosome interferes with meiosis and
prevents individuals from reproducing
- some cases have shown genotypes of XXXY or XXXXY
- no babies are born without an X chromosome, indicating
the X chromosome contains genes necessary for development
- sex chromosome abnormalities show the role of the Y
chromosome in sex determination
- a small region of the Y chromosome is necessary to
produce male sexual development, even if combined with several
X chromosomes
- if the sex determining region is missing from the Y
chromosome, the child develops as a female
14-3 Human Molecular
Genetics
A. Human DNA analysis
- there are about 6 million base pairs in our DNA
- biologists must use special techniques to read DNA
sequences to look for information they need
1. Testing for alleles
- used when looking for disorders that contain DNA
sequences that are slightly different from the normal condition
Ex. cystic fibrosis and Tay-Sachs disease
- DNA probes are used to find specific sequences in
disease-causing alleles
- Some tests look for changes in restriction enzymes or
differences in length of normal and abnormal alleles
- There are genetic tests for many disorders to determine if
parents risk passing abnormal alleles to their children
- DNA testing can tell exactly what the genetic problem
causing the disorder is, making it easier to treat
2. DNA Fingerprinting
- no individual is exactly like any other genetically;
except identical twins
- DNA fingerprinting is a powerful tool used to
identify individuals by analyzing segments of DNA that
have little or no known function, but that vary widely among
individuals (See Fig 14-18)
- Used to determine whether blood, semen, or other
material left at a crime scene matches the DNA from a
suspect
- Used since late 1980s in U.S. ; very reliable
B. The Human Genome Project
- an attempt to sequence all human DNA begun in
1990
- the genome of several other organisms was also
completed including yeast and the fruit fly
- the human genome was completed in June of 2000
Searching for Genes
- the hunt for genes continues today through 24
volumes of information (22 autosomal and 2 sex
chromosomes)
A Breakthrough for Everyone
Genome research data is available to everyone and can be found on the
internet
(See www.phschool.com for direct link to latest information)
C. Gene Therapy
- an absent or faulty gene is replaced by a normal, working gene
- can be used to correct genetic disorders
- the normal gene can make the correct protein or enzyme and
eliminate the cause of the disorder
- viruses are modified so they do not cause disease and
genetically engineered to carry the normal gene into the individual’s
cells (See Fig 14-21)
- not totally successful; it remains a high-risk and experimental
procedure
D. Ethical Issues in Human Genetics
- guidelines must be instituted as to what should and
should not be done with the human genome
- this is a societal issue and does not remain solely in
the hands of researchers