Genes and Medical Genetics

Chapter 2

Genotype and Phenotype

Genotype = all the genes that an individual has

Phenotype = physical appearance of the individual

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Genotype (con’t)

– Alleles can be dominant (capital letter) or recessive (lower case letter).

– Alternate forms of a gene having the same position (locus) on a pair of matching chromosomes that control the same trait are called alleles

– An individual has two alleles for each trait because a chromosome pair carries alleles for the same traits

– How many alleles for each trait will be in the gametes?

Example – in humans unattached earlobe is dominant over attached earlobes

• Could use capital E to show dominant allele and lower case e to show recessive (non-dominant) allele

Note: it is customary to designate alleles by the same letter, with uppercase to signify dominant and lowercase to signify recessive Fig. 02-01

• When the two alleles are both dominant it is called a homozygous dominant genotype– The phenotype will be

unattached earlobes

• When the two alleles are both recessive it is called homozygous recessive– The phenotype will be

attached earlobes

• When the two alleles are different (one dominant, one recessive) it is called a heterozygous genotype– The phenotype will be

________________.

Fig. 02-01

Forming gametes (gametogenesis)

• Recall: gametes have ½ normal # of chromosomes

• Happens when chromosome pair separates during meiosis

• Since alleles are on chromosomes, they also separate during meiosis, thus gametes only carry one allele for each trait.– Ex. If individual was Ee, and

produced four gametes, ½ would be E and ½ would be e.

(Chromosomes already doubled)

Fig. 02-02 Gametogenesis

Fig. 02-03

CommonInheritedCharacter-istics inHumans

Phenotypes

Genotypes

WW or Ww ww

EE or Ee ee

SS or Ss ss

FF or Ff ff

Genetic Crosses(One-trait Crosses)

• If know genotype of parents, can predict chances of having a child with certain genotypes (and thus certain phenotypes).– Ex. If one parent is homozygous dominant (EE)

the chance of having a child with unattached earlobes is 100% because parent only has dominant allele (E) to pass on to baby.

– But, if both parents are homozygous recessive (ee), the chance of having a child with attached earlobes is 100% because parents only have recessive allele (e) to pass on to baby.

One-trait Crosses (con’t)• If both parents are

heterozygous (Dad is Ee, and Mom is Ee), what are the chances that baby will have unattached or attached earlobes?

• Determine using a Punnett Square

• Each child will have a 75% chance of dominant phenotype (unattached), and 25% chance of having recessive phenotype (attached).

Fig. 02-04 Heterozygous-by- Heterozygous cross

Punnett

Square

• What if one parent is Ee and the other is ee?

• Each child will have a 50% chance of having unattached earlobes

One-trait crosses (con’t)

Fig. 02-05 Heterozygous By Homozygous cross

Punnett

Square

Genetic Crosses(Two-trait Crosses)

• What if want to look at two traits at the same time? – Ex. Widow’s peak (W) and short fingers (S)

(both dominant traits).

• If one parent is homozygous for widow’s peak and short fingers (WWSS) and other is homozygous for straight hairline and long fingers (wwss), what will– Children look like?– Grandchildren look like?

Fig. 02-06 Dihybrid cross using Punnett

Square

• Expected phenotypic ratio for a dyhibrid cross is always 9:3:3:1

• Can use this expected ratio to predict chances of each child receiving a certain phenotype– Ex. Chance of getting

two dominant phenotypes together is 9 out of 16

– Chance of getting two recessive phenotypes is 1 out of 16

Autosomal Dominant Disorders

• Genetic disorders are caused by mutations• Mutations – permanent changes in genes (DNA)• If disorder is autosomal dominant mutation is

a single allele, and heterozygotes will exhibit the disorder

• If know genotype of parents, can determine chances of children having the disorder (see Table 2.2, p. 26)

• Can provide genetic counseling to parents who can make decision about best courses of action (Chapter 4).

Autosomal Dominant Disorders

• Neurofibromatosis– Most common genetic disorders (1 in 3,500 newborns,

all races and ethnicities)– Symptoms

• Large tan spots on skin that get darker with age• Small, benign (?) tumors (neurofibromas) often occur in nerves• If severe case

– Skeletal deformities (including a large head)– May develop eye and ear tumors become blind and deaf

• Children with non-severe symptoms may still have learning disabilities and be hyperactive

– Gene for neurofibromatosis has been located on chromosome 17

– Found that gene controls production of protein that usually blocks cell growth

– If gene not working certain cells grow out of control =_______________ .

Autosomal Dominant Disorders• Huntington Disease

– Neurological (nervous system) disorder that causes progressive degeneration of brain cells.

– Symptoms• Most patients appear normal until middle age (may already

have children)• Severe muscle spasms• Personality disorders

– Treatment – none (patients die in 10 – 15 years after symptoms appear)

– Gene (mutated) located on chromosome 4 causes abnormal protein that clumps inside neurons (nerve cells)

– Test developed for presence but most people do not want to know– Two minute paper: “Would you want to be tested for a fatal genetic

disease?

Why or why not?”

Autosomal Recessive Disorders

• Cystic Fibrosis (CF)– Most common lethal genetic disease among

Caucasians in the US– 1 in 20 are a carrier, 1 in 2,500 newborns has it– Caused by defect in plasma membrane (gene

on chromosome 7)– Symptoms

• Thickened mucous in bronchial tubes (problems breathing) and pancreatic duct (problems digesting)

– Treatment – mucous in lungs manually loosened and other treatments have raised life expectancy to 35-40 years old

Fig. 02-08 Treatment for CF

Autosomal Recessive Disorders

• Phenylketonuria (PKU)– Not so common as CF– Affects nervous system development

• Caused by missing enzyme that normally allows metabolism of the amino acid phenylalanine

• Causes abnormal breakdown product (phenylketone) in urine

– Symptoms – severe mental retardation, black urine

• PKU allele located on chromosome 12 prenatal DNA test can detect it (and elevated phenylalanine in blood)

• If detect place newborn on diet low in phenylalanine until at least age 7

Autosomal Recessive Disorders

• Tay-Sachs Disease– Usually occurs in Jewish people– Symptoms

• Development slows at age 4 to 8 months• Neurological and Psychomotor impairment• Child gradually becomes blind and helpless,

seizures, paralyzed, death by age 3 – 4 years old

– Caused by gene on chromosome 15 caused buildup of nonfunctional lysosomes in neurons

Autosomal Recessive Disorders

• Albinism– Person unable to produce

pigment melanin colors skin, hair, eyes

– Symptoms• White hair, pink eyes, super-

white skin• Vision problems

– Example of epistasis one gene affects the expression of other genes

• In albino any gene for coloring cannot be expressed because mutated gene prevents them from producing melanin

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