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

Example Map Problem• A kidney-bean-shaped eye is produced by a recessive gene k on the third chromosome of

Drosophilia. Orange eye color, called "cardinal," is produced by the recessive gene cd on the same chromosome. Between these two loci is a third locus with a recessive allele e that produces ebony body color. Homozygous "kidney," cardinal females are mated to homozygous ebony males. The trihybrid F1 females are then testcrossed to produce the F2. Among 4000 F2 progeny are the following:

1761 Kidney, Cardinal 97 Kidney1773 Ebony 89 Ebony, Cardinal128 Kidney, Ebony 6 Kidney, Ebony, Cardinal138 Cardinal 8 Wild type (+)

• (a) Determine the linkage relationships in the parents and F1 trihybrids.• (b) Estimate the map distances.

a) Female(kk e+e+ cdcd) X Male (k+k+ ee cd+cd+)F1= kk+ ee+ cdcd+(wild type)

b) ke crosses: k e (128) and cd (138)double crosses: k e cd (6) and wild type (8)128+138+6+8= 280/4000 x 100= 7% = 7mu

ecd crosses: e cd (89) and k (97)double crosses: k e cd (6) and wild type (8)89+97+6+8= 200/4000 x 100 = 5% = 5mu

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– ⃝V 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