Post on 23-Feb-2016
description
Human GeneticsCh. 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 X-recessive
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– ⃝T 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) Deletion2) Duplication3) Translocation4) 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