Transcript Human Genetics Ch. 13.1-13.4

Human Genetics
Ch. 13.1-13.4
Why Study Our DNA?
• Learn the effects of mutations
• Understand how genetic
diseases are generated
• Propose possible treatments
for genetic diseases
• Identify causes of genetic
diseases
• Unfortunately, inheritance is
mostly NON-Mendelian
– The alleles for traits are passed
on and expressed in complex
ways
Genetic Linkages
• What is Mendel’s Principle of
Independent Assortment?
– Genes are separated independently
into gametes and thus offspring
• We have only 23 chromosomes,
why is complete independent
assortment impossible?
– 100,000 of genes and only 23
chromosomes to be condensed
into; some genes have to share the
same chromosome
• Genes on the same chromosome
are linked genes
• In order to study inheritance of
multiple genes, we are going to
have to map out what genes are
on what chromosomes
Mapping A Chromosome
• Morgan and Sturtevant; 1900’s
– Cross-breeding fruit flies;
Drosophila melanogaster (model
genetic studies organism)
• pr+pr+ vg+vg+ red eyes; long
wings
– “+” = wild type (normal/dominate)
• prpr vgvg purple eyes; vestigial
wings
• Expected 1:1:1:1 ratio (all
combinations of eye color and
wing type)
• Got almost 1:1 of parental
phenotypes (Red/Long:
Purple/Vestigial
• Small percent were Red/Vestigial
or Purple/Long (recombinant
phenotype)
Mapping A Chromosome
• Why a near 1:1 of the parental
phenotypes?
– Genes are linked; eye color and
wing type are on the same
chromosome
• Why the small percent of
recombinant phenotype?
– Crossing Over during meiosis;
Genes must have been switched
on homologous chromatids
• If two sections of a chromosome
are switching places, than what
can you conclude about the
percent of genes you would see
switched in an organism?
– The further away the genes are
from each other on the
chromosome the more likely they
will get switched
Recombinant Frequencies
• Of the F1 generation; 305 had
recombinant phenotypes of
the 2,839 total progeny
(offspring). What is the
recombinant frequency?
– 10.7% (305/2,839 *100)
• Sturtevant brilliantly deduced
that recombinant frequencies
between multiple linked genes
could be use to map out the
locations of genes on their
chromosome
– <1% - 50%; Why is 50% the
max?
• Progeny get either parental
chromosomes or recombinant
chromosomes (50%)
– Linkage map
Linkage Map
• Written in mu (map units) or cM
(centimorgan); map shows relative
location based on other known alleles
• Map of alleles a, b, and c:
– a-b 9.6% = 9.6 mu
– b-c 2% = 2 mu
– a-c 8% = 8 mu
• a must be far from b and c must be
between them, but much closer to b
– 9.6 mu (a-b)– 2 mu (c-b)= 7.6 mu (a-c)
– Why the inconsistency?
– a is pretty far from c and b so there may
be a double cross over sometimes
• What can we conclude about genes
more the 50 mu apart?
– They follow independent assortment (no
linkage) because 50% is highest possible
recombinant frequency
The Amazing Drosophila
• Genes linked to sex
chromosomes also discovered
through fruit flies
• Doing a F2 cross Morgan expect
the normal 3:1 but instead he got
all females with red eyes and
50% males with white or red
eyes
• What does this tell us?
– Eye color is sex linked; X
chromosome
– Males have a 50% of getting Xw+ or
Xw; females all get at least one Xw+
so they all have red eyes
– X-linked recessive all males
progeny of a XrXr x YXR get Xr
Sex-Linked Genes
• Any genes located on the sex
determining chromosomes
– X or Y in humans
– Mapped through male/female
dependent inheritance
– All other 22 chromosomes are
called autosomes (automatically
inherited)
• Y Chromosome
– Sex-determining genes; SRY gene
makes females into males while
an embryo
– Maybe fading from existence;
may be getting smaller
– XY heterogametic
• X Chromosome
– Mostly codes for non-sex related
traits (ex. Color vision)
– XX homogametic
Too Many Xs!
• Why do females need two Xs?
– They Don’t! Two X chromosomes
would mean double the genetic
material necessary
• What does the body do with the
X chromosome?
– It randomly shuts one X down
– Creates a Barr body dense
mass of inactive chromatin
– They are copied and passed on in
mitosis but are never used for
proteins
• How can this show us Xrecessive traits?
– Dominate X might be randomly
deactivated so the X recessive is
randomly present in cells
– Female calico cats have a mix of
orange and black fur but males
are always black or orange
Following Sex-linked Traits
• Pedigree map of parents
and offspring in a family over
generations
–
–
–
–
⃝ female
 males
 has trait
 carrier; has gene but not
trait
• Hemophilia platelets
numbers so low person often
bleeds to death from little
body damage
– X-linked recessive gene
– Rare for XhXh why?
• Most males with the disease do
not reproduce
– Lead to the Russian Revolution
Chromosomal Mutations
• Major change in a
chromosome's structure
or the number of
chromosomes in a
gamete
• 4 Types:
1) Deletion
2) Duplication
3) Translocation
4) Inversion
Deletions and Duplications
• Deletion section of
chromosome is lost
– Cri-du-chat (cat’s cry)
– Deletion from Chromosome 5
causes mental retardation and
malformed larynx
– Cry sounds like cat meow
• Duplication section is inserted
to a homolog that already has
that section
– Why can two copies allow the
slow testing of mutations?
– One mutated copy tests
adaptation but organism
basically functions normally
– Hemoglobin in humans has
evolved this way
Translocation and Inversion
• Translocation section
attached to non-homolog
– Typically reciprocal (two
chromosomes each have
translocation)
– Philadelphia Chromosome
translocation of 9 and 12;
causes uncontrolled growth in
white blood cells (leukemia)
• Inversion section attached
to original chromosome but
in the reverse order
– Genes lose function or
produce harmful/beneficial
new versions
Non-Disjunction
• Euploidy normal amount of
chromosomes
• Aneuploidy missing or extra
amount of chromosomes
– Monoploids, triploids, tetraploids,
….polyploids
• Most miscarriages (baby deaths
before birth) are aneuploidy
• Trisomy 21 and 18 develop but
live short and difficult lives
• X and Y polyploidy survive…
– XYY?
– Extra Y’s just mean more male
characteristics; no essential genes
– XXY and XXX?
– Barr bodies turn off extra Xs
Human Inheritance Patterns
• Autosomal Recessive
– RR no trait
– Rr carriers
– rr show the trait
• CF Cystic Fibrosis
– 1:4,000 births in US
– Lose Cl- channel transport efficiency
– Build up of thick mucus blocks lungs
and promotes disease
• PKU Phenylketonuria
– 1:15,000 births in US
– Enzyme cannot break phenylalanine
into tyrosine
– Build up causes brain damage
– Must be medicated and restrict diet
Human Inheritance Patterns
• Autosomal Dominate
– RR have trait
– Rr have trait
– rr no trait
• Dwarfism
Achondroplasia
– 1:25,000 births worldwide
– Only heterozygous survive
embryo development
– Defective cartilage leads to
short arms and legs; large
heads; regular sized body
Human Inheritance Patterns
• X-Linked Recessive
– XX no trait
– XXr carries
– XrXr have trait
• DMD Duchenne muscular
dystrophy
– Muscle tissue degrades; most cannot
walk or need crutches
– Dystrophin is defective; protein anchor
in muscle cells; results in tearing
• X-Linked Dominate
–
–
–
–
–
XX have trait
XX have trait
XrXr no trait
Extremely rare in humans
Teeth discoloration
Genetic Disease Testing
• YOUR TURN!
• Write a 2 page essay (12 size
arial font, normal margins) on 3
methods used today to test for
genetic diseases
– Two may come from your book
– One MUST come from an outside
source
– You essay should have details in
how the process works and the
pro and cons (good and bad
parts)
• Essay is due 12/13, in print
Homework
• Actual:
– Essay on Genetic Screening
– Fruit Fly Lab
– Apply Evolutionary Thinking
(p.280)
• Suggested:
– Test Your Knowledge (Ch. 13)
– Design the Experiment (Ch. 13)
• Test on Ch. 11, 12, and 13 on
Thursday