Ch.5 Beyond Mendel’s Laws

5.1

Lethal Alleles Lethal genotypes- death before alleles are

passed on. Before reproduction. Exception- Huntington’s disease-

Begins at age 30-40. Lethal alleles- spontaneous abortions If both parents are heterozygous-

25 % chance of being homozygous recessive. Homozygous dominant- lethal in embryos

Ex. Mexican hairless dogs.

Incomplete Dominance

Heterozygous phenotype is intermediate between each homozygote.

Human Ex. TaySachs- intermediate enzyme level in

heterozygotes. Human hair curliness

SS=straight, ss=curly, Ss=wavy FH-Familial hypercholesterolemia

A heterozygote has half the number or receptors for LDL cholesterol in the liver with intermediate plasma cholesterol levels.

Classic Snapdragons use C= color

RR= Red CRCR rr= white(WW); CWCW Rr (RW)= pink; CRCW

P1 CRCR x CWCWF1 CRCW x CRCWF2 CRCR CRCW CWCW 1:2:1

red pink white Same genotypic and phenotypic

ratios

Codominance: Both alleles are experessed in a

heterozygote. AB Blood Type ABO Blood types:

Determined by cell surface antigens Antigen- protein with attached sugar on plasma

membrane of red blood cells Type A- A antigen Type B- B antigen Type O- no sugar antigen Type AB- both A and B antigens

Codominance examples-

Both alleles are expressed equally Example-

is red and white striped flowers Roan cattle

Multiple alleles 1 gene; more than 2 allele forms Examples-

Acyl CoA dehydrogenase deficiency Mitochondria- affects heart and skeletla

muscles. Other alleles lessen severity producing some

enzyme. PKU- buildup of phenylalanine

More than 300 mutant alleles-4 phenotypes Classic PKU- profound mental retardation Moderate PKU Mild PKU Excrete excess phenylalanine in urine Correlation of genotypes with phenotypes – to

monitor diet and predict outcome.

Cystic Fibrosis-

Several hundred alleles 70% of cases- F508 homozygous Many variations Pancreatic function correlates better

than lung symptoms.

Blood types Phenotypes- Blood

Types (4) ABABO

Genotypes (6)

IAIA or IAiIBIB or IBiIAIBii

Blood Typing: ABO blood group:

Antigens are on the rbcs. Antibodies to other antigen sugar types circulate in

the plasma portion of blood. Blood Type A- has anti B in plasma. Blood Type B- has anti A in plasma Blood Type O- has anti A,B in plasma Blood type AB- no anti A or anti B

Blood Type O- universal donor because there are no A or B antigens.

Blood type AB- universal recipient, since no antibodies to A or B.

To type a person’s blood- the rbcs are mixed with different antibody sera. Clumping indicates the presence of the corresponding antigen on the red blood cells. Ex Antigen A clumps with antiA sera.

Rh Factor- Named for rhesus monkeys where found. The main factor is a D antigen found on the red blood

cells. Unlike ABO blood types, antibodies are only present if

an Rh negative person is exposed to Rh positive blood cells.

85 % pop. Has the D allele=Rh + 15% pop. Is recessive dd= Rh- Rhogam- anti D is given to Rh- mothers to bind any

fetal Rh + red blood cells if there is a bleed to prevent the mom from making circulating antibodies to the fetus’ red blood cells.

Hemolytic Disease of the newborn results from this imcompatibility. – can result in death.

EpistasisOne gene affects the expression of a second gene

Example: H gene is epistatic to the ABO gene.• H protein attaches a molecule to the cell surface

to which the A or B antigens are attached• hh genotype = no H protein= • Without H protein the A or B antigens can not be

attached to the cell• All hh genotypes have the phenotype of type O,

although the ABO blood group can be anything (A, B, AB, or O)

Bombay phenotype-identified in 1952- Bombay, India Very rare example of epistasis Individuals phenotype= Blood type O However they have no H antigen so they

have antibodies to H (anti-H), antibodies to A (anti-A) antibodies to B (anti-B) in their circulating plasma.

Bottom line- they will be incompatible with all blood types; even O

Can only receive their own blood; or another Bombay’s.

Incomplete Penetrance The phenotype is not always observed

among individuals carrying the genotype – express or not DD or Dd - only 80% show polydactyly

Variable Expressivity

• A phenotype that varies in intensity Polydactyly two extra digits on each hand and foot vs. one extra digit on one foot Individuals with the same genotype for familial hypercholesterolemia have varying levels of symptoms

PleiotropyOne gene has many

symptoms or controls several functionsExample: porphyria

variegata

Photo © North Wind Picture Archives

Figure 5.5a

Figure 5.5b

Genetic Heterogeneity

• Different genes can produce identical phenotypes

Hearing loss Osteogenesis imperfecta

• Genes may encode for different enzymes in a biochemical pathway

Clotting disorders

Phenocopy Appears inherited but is caused by the

environment May have symptoms that resemble an inherited

trait or occur within familiesExamples: Exposure to teratogens

Thalidomide causes limb defects similar to inherited phocomelia

Hydroquinone exposure looks like alkaptonuria

Infection AIDS virus can be passed from mother to

child, looking like it is inherited

Importance of Human Genome Sequence

Complications to Mendelian inheritance more common than originally thought

Overlapping of definitions – Marfan syndrome has both epistasis and genetic heterogeneity

Table 5.3

Mitochondrion Organelle providing cellular energy Contains small circular DNA No crossing over or DNA repair High exposure to free radicals Mutation rate is greater than nuclear DNA 37 genes without noncoding sequences Mitochondrial genes are transmitted from

mother to all of her offspring

Mitochondrial Inheritance

Figure 5.8

Mitochondrial DNA pedigree

Mitochondrial Disorder Examples

Mitochondrial myopathies – weak muscles

Leber optic atrophy – impairs vision

Ooplasmic transfer technique can enable woman to avoid transmitting a mitochondrial disorder

Heteroplasmy Many copies of the mitochondrial

genome per cell

May have more than one allele for the same gene in the same cell

Heteroplasmy is the condition where mitochondrial DNA sequence is not the same in all copies