From genotype to phenotype

 Genes act in the context of the environment, and

sometimes in concert with other genes
 Environmental-influenced phenotypes:
- Shibire mutation in D. melanogaster (Factor:
temp.)
 Culture@ 25 ºC: viable and fertile flies
 Culture@ 25 ºC + shake: temporarily paralysed
 Culture@ 29 ºC: fall & die
- Phenylketunoria (PKU) (Factor: Diet)
 recessive disorder of amino acid metabolism
 homozygous infants – accumulate toxic substance – mental
impairment
 phenylalanine diet (less, clinical impact reduced)

Prof Sam CK-Basic genetics

 From genotype to phenotype
 Environmental-influenced phenotypes:
- Pattern baldness in Humans (Factore: Gender)
 In Male – testosterone
Male Female
BB bald bald
Bb bald non-bald
bb non-bald non-bald

 sex-influenced

Prof Sam CK-Basic genetics

 Penetrance & Expressivity
 Penetrance : the percentage of individuals
with a given genotype who exhibit the
phenotype associated with that genotype.
- a gene is expressed or not
- incomplete penetrance = individual Q
- complete penetrance = Q’s 2nd & 3rd kids

Prof Sam CK-Basic genetics

 Penetrance & Expressivity
 Eg. of Penetrance
- polydactyly (from one limb to 4 limbs)

Prof Sam CK-Basic genetics

 Penetrance & Expressivity
 Expressivity : the level of expression of a
mutant phenotype
- Lobe eye mutation in D. melanogaster

Prof Sam CK-Basic genetics

 Variably expressed genes
 May show complete or incomplete
penetrance
 Example 1: dominant Lobe gene in D.
melanogaster
- expressed in 75% of heterozygous flies (75%
penetrance)
- vary from complete absence of eyes to
normal size (variable expression)

Eyeless fly
Prof Sam CK-Basic genetics
Variable expressivity of Lobe
mutation in Drosophila

Prof Sam CK-Basic genetics

 Variable penetrance in
expression of Lobe
mutation in Drosophila

Partial
Wild type
reduction

Eyeless

Prof Sam CK-Basic genetics

Variable expression & penetarnce
 Example 2: dominant allele P
- polydactylous condition in only a proportion of
heterozygotes (incomplete penetrance), and the
expression varies from being in one limb to all 4
limbs (variable expressivity)

Prof Sam CK-Basic genetics

Polydactylous

Prof Sam CK-Basic genetics

 The Hapsburg Jaw

• Mandibular prognathism: A proturusion of the mandible often

associated with difficulty in chewing

• A dominant trait with incomplete penetrance and variable expressivity

• Middle Ages – the beginning of 20th Century: House of Hapsburg ruled

Europe (much of it)

• Austria, Spain, Italy (among others)

• Mode of Conquest: Bella gerant allii, tu, felix Austria, nube! “Let
others wage wars; you happy Austria, marry!”
Hapsburg Jaw

Prof Sam CK-Basic genetics

Can you find where this family is
inbreeding?
Inbreeding
The Hapsburg Jaw
• Spread gene = spead phenotype

• How people detect this?  portraits of the Hapsburg:

coins, paintings, suculptures recently…photographs.
Charles II (1161-1700), the last Habsburg
•1st documented case among the Hapsburg: Emperor King of Spain had the most extreme case of
Maximilian I of Austria Habsburg Jaw recorded. He was also mentally
disabled. An analysis of the previous
marriages that led to his birth reveals multiple
•Phillip I (Max’s son ) x Joanna (the Mad, Spain)  uncle-niece marriages and first cousin
marriages.
becomes king of Spain This coin of Leopold I
- HJ manifestation? Not sure but… (1640-1705), another
Habsburg, again shows
the characteristic
•Phillip I’s son = Charles V has HJ , severe  mouth Habsburg Lip. However,
some coin collectors do
hang open not believe that this coin
(lives in Flanders – went to Spain Spain became the is accurate.
most powerful country)
Habsburg jaw or lip had
• Phillip II (Charles V’s son) has HJ been passed through
generations of the family for
as far back as 1421 when a
•Phillip III (Phillip II’s son) not sure but Phillip IV jutting jawed princess
(Phillip III’s son) has HJ – Spanish line ENDed with Zimburg of Masovia
Carlos/Charles II (1700; Phillip IV’s son) married one of the
Habsburg princes.
The Hapsburg Jaw

Maximillian I of Charles V of Spain Phillip IV of Spain

Austria (1500-1558)
(1459-1519)
BUT …
•Carlos II appointed Phillip of Anjou (House of Bourbon, French) as his successor
Because Bourbons had married Hapsburgs in previous generations, some of the Spanish
Bourbons inherited the Hapsburg Jaw….eg. Alfonso XIII
Inbreeding

(Carlos II)
 Phenocopy
 Produced by environment that stimulates
effects of particular gene or group of genes
 Stimulated phenotype is not inherited
 E.g., intake of thalidomide during early
pregnancy stages
- malformed babies with phocomelia

Prof Sam CK-Basic genetics

Thalidomide babies

Prof Sam CK-Basic genetics

 Pleiotropy
 When a gene has multiple phenotypic effect
 Single mutation may affect many traits
 Example 1: Phenylketonuria (PKU)
 Example 2: Bristle formation in D.
melanogaster
(affecting female fertility but not
male’s)

Prof Sam CK-Basic genetics

 Bristle morphology of Drosophila
melanogaster

Wild-type bristles

Singed bristles
Prof Sam CK-Basic genetics
 Conditional mutants
 Expression only under certain conditions
1. Auxotrophs
2. Phenylketonuria (PKU)
3. Lactose intolerance

Prof Sam CK-Basic genetics

Onset of genetic expression
 Tay-Sachs disease [abnormal GM2 ganglioside
accumulation in nerve cells (brain)]: 6 months old, death
by 4 years old
 Lesch-Nyhan Syndrome [deficiency of the enzyme
hypoxanthine-guanine phosphoribosyltransferase (HGPRT), in
chromosome X  uric acid accumulation  kidney & gout prob,
intellectual disability]: 2yr
 Duchene muscular dystrophy [ no dystrophin 
muscle degeneration] :<6yr

 Huntington disease [ extra CAG repeats  damage cells

in the brain: usually 35 - 44 yr Prof Sam CK-Basic genetics
Tay-Sachs disease

Prof Sam CK-Basic genetics