4 Mendel & The Gene Idea

I. GREGOR MENDEL’S DISCOVERIES  EXPERIMENTAL AND QUANTITATIVE APPROACH  PARTICULATE THEORY OF INHERITANCE BASED ON EXPERIMENTS WITH GARDEN PEAS, CARRIED OUT IN THE 1860S..

Mendelian genetics 4 Character (heritable feature, i.e., fur color) 4 Trait (variant for a character, i.e., brown) 4 True-bred (all offspring of same variety) 4 Hybridization (crossing of 2 different true- breds) 4 P generation (parents) 4 F1 generation (first filial generation)

Genetic vocabulary……. 4 Punnett square: predicts the results of a genetic cross between individuals of known genotype 4 Homozygous: pair of identical alleles for a character 4 Heterozygous: two different alleles for a gene 4 Phenotype: an organism’s traits 4 Genotype: an organism’s genetic makeup

ALLELES, CONTRASTING VERSIONS OF A GENE

Law of Segregation 4 For each character, an organism inherits 2 alleles, one from each parent 4 The alleles for each character segregate (separate) during gamete production (meiosis).

Law of Independent Assortment 4 Law of Segregation involves 1 character. What about 2 (or more) characters? 4 Monohybrid cross vs. dihybrid cross 4 The two pairs of alleles segregate independently of each other.

TESTCROSS

MENDELIAN INHERITANCE REFLECTS RULES OF PROBABILITY 4 PRODUCT RULE : THE PROBABILITY OF A COMPOUND EVENT IS EQUAL TO THE PRODUCT OF THE SEPARATE PROBABILITIES OF THE INDEPENDENT SINGLE EVENTS. 4 Example: –the probability of 3 girls born to a family = 1/8 –1/2 x 1/2 x 1/2 = 1/8

Non-single gene genetics 4 Incomplete dominance: appearance between the phenotypes of the 2 parents. Ex: snapdragons 4 Codominance: two alleles affect the phenotype in separate, distinguishable ways. Ex: Tay-Sachs disease 4 Multiple alleles: more than 2 possible alleles for a gene. Ex: human blood types

Non-single gene genetics 4 Pleiotropy: genes with multiple phenotypic effect. Ex: sickle-cell anemia 4 Epistasis: a gene at one locus (chromosomal location) affects the phenotypic expression of a gene at a second locus. Ex: mice coat color 4 Polygenic Inheritance: an additive effect of two or more genes on a single phenotypic character Ex: human skin pigmentation and height

Pleiotropy

Epistasis One gene alters the expression of another gene.

Polygenic Inheritance

MENDELIAN INHERITANCE IN HUMANS

 PEDIGREE ANALYSIS REVEALS MENDELIAN PATTERNS IN HUMAN INHERITANCE  FAMILY PEDIGREES CAN BE USED TO DEDUCE THE POSSIBLE GENOTYPES OF INDIVIDUALS AND MAKE PREDICTIOM ABOUT FUTURE OFFSPRING.  ANY PREDICTIONS ARE USUALLY STATISTICAL ABILITIES RATHER THAN CERTAINTIES

Key

1.Autosomal Dominant 4 (i) seen in every generation 4 (ii) males and females have condition 4 (iii) unaffected parents do not have children with the condition 4 (iv) each child of an affected individual has a 50% chance of being affected

Autosomal Dominant

2.Autosomal Recessive 4 (i) typically appears in one generation but not their parents 4 (ii) males and females are equally affected 4 (iii) both parents are heterozygotes 4 (iv) each unaffected full sibling of an affected individual has a 2/3 chance of being a carrier

Autosomal Recessive

3.Sex-linked Recessive (i) Males are almost exclusively affected. (ii)No father to son transmission occurs but all daughters of affected fathers will be carriers. (iii)Carrier females have a 50% or 1 in 2 chance of having an affected son and a 50% or 1 in 2 chance of having a carrier daughter. (iv)The affected son may inherit the changed gene from a carrier mother

Sex-linked Recessive

Recessively Inherited Disorders 4 usually caused by defective alleles that code for a malfunctional protein or no protein 4 herterozygotes are usually phenotypically normal (the condition is expressed in homozygotes born from heterozygote parents)

4 most common lethal genetic disease in NA. Affects 1 in 2500 Caucasians 4 normal dominant allele codes for membrane protein that pumps chloride ions out of cells. 1.Cystic Fibrosis

4 pumps are lacking in CF homozygotes so chloride accumulates abnormally in the cells causing an uptake of water from the surrounding mucus. 4 results in a thickened mucus that builds up in the pancreas, lungs and digestive tract

2.Tay-Sachs Disease 4 affects 1 in 3600 births (about 100 times higher in the European Jewish population) 4 brain cells are unable to metabolize lipids because a crucial enzyme functions improperly

4 as lipids accumulate on the brain, the infant suffers seizures, blindness, degenerated moter and cognitive capacity. 4 child usually dies after a few years.

3.Sickle Cell Anemia 4 most common inherited disease among African Americans (1 in 400) 4 caused by a single amino acid substitution in hemoglobin (valene for glutamic acid)

4 red blood cells deform from a normal disk shape to a sickle shape. 4 the sickled cells clog tiny capillaries 4 heterozygous advantage for malaria

Dominantly Inherited Disorders 4 Example:Achondroplasia (dwarfism) –L 1 in 10,000 heterozygous –L homozygous dominant results in spontaneous abortion of the fetus

Lethal Dominant Genes 4 very rare since the individuals do not survive to reproductive age.

Late-acting Lethal Dominant Genes 4 can escape elimination from the population if the disorder does not appear until an advanced age (after the individual has passed on the gene to their children) –ex: Huntington’s Disease

Huntington’s Disease 4 degenerative nerve disease 4 effects appear between 35 and 40 4 children of an afflicted parent have a 50% chance of inheriting the lethal dominant allele.

Detecting Genetic disorders

1. Genetic counseling 4 provide information to prospective parents 4 it is generally a “preventative” approach and often involves risk management

2. Carrier recognition 4 Several tests are currently available for the following: –Tay-Sachs –CF –sickle-cell anemia

3. Fetal Testing 4 Amniocentesis 4 Chorionic Villi Sampling 4 Ultrasound 4 Fetoscopy 4 Newborn Testing

Amniocentesis 4 withdrawing and testing amniotic fluid 4 chemicals within the amniotic fluid may indicate a disorder 4 cells grown in culture from fetal cells may indicate a disorder (may take several weeks).

Chorionic Villi Sampling –a small amount of fetal tissue is suctioned off the chorionic villi of the placenta. –cells are embryonic in origin and are dividing rapidly. –This allows karyotyping to be carried out immediately (results in 24 hours). –can be performed earlier than amniocentesis

Ultrasound 4 non-invasive, no known risk to fetus

Fetoscopy 4 involves inserting a thin fiber-optic scope into the uterus.

Newborn Testing 4 in most hospital routine tests are performed at birth –Example:phenylketonuria (PKU)

PKU –1 in 15,000 births –cannot breakdown the amino acid phenylalanine –phenylalanine and its byproduct (phenylpyruvic acid) accumulate to toxic levels in the blood, causing mental retardation. –early screening ca detect the deficiency and an altered diet (low in phenylalanine) can prevent retardation.