GREGOR MENDEL

• 1860’S- AUGUSTINIAN MONK• DISCOVERED THE FUNDAMENTAL

PRINCIPLES OF HEREDITY• PARTICULATE THEORY OF HEREDITY =

MENDEL’S THEORY THAT PARENTS TRANSMIT TO THEIR OFFSPRING DISCRETE INHERITABLE FACTORS (GENES) THAT REMAIN AS SEPARATE FACTORS FROM ONE GENERATION TO THE NEXT

TERMS TO KNOW

• CHARACTER = DETECTABLE INHERITABLE FEATURE

• TRAIT = VARIANT OF AN INHERITABLE CHARACTER

• TRUE BREEDING = ALWAYS PRODUCE OFFSPRING WITH THE SAME TRAITS AS THE PARENTS WHEN PARENTS ARE SELF FERTILIZED

A GENETIC CROSS

3 GENERATIONS OF PEA PLANTS

MENDEL’S HYPOTHESES• 1) ALTERNATVE FORMS OF GENES ARE

RESPONSIBLE FOR VARIATIONS IN INHERITED CHARACTERS

• 2) FOR EACH CHARACTER, AN ORGANISM INHERITS TWO ALLELES, ONE FROM EACH PARENT

• 3) IF THE TWO ALLELES DIFFER, ONE IS DOMINANT, THE OTHER RECESSIVE

• 4) THE TWO ALLELES FOR EACH CHARACTER SEGREGATE DURING GAMETE PRODUCTION

LAW OF SEGREGATION

• ALLELE PAIRS SEGREGATE DURING GAMETE FORMATION (MEIOSIS), AND THE PAIRED CONDITION IS RESTORED BY THE RANDOM FUSION OF GAMETES AT FERTILIZATION

ALLELES

LAW OF SEGREGATION

TERMS TO KNOW

• HOMOZYGOUS = HAVING TWO OF THE SAME ALLELES (PP)

• HETEROZYGOUS = HAVING TWO DIFFERENT ALLELES (Pp)

• PHENOTYPE = AN ORGANISM’S EXPRESSED TRAITS (PURPLE FLOWERS)

• GENOTYPE = AN ORGANISM’S GENETIC MAKE-UP (PP, Pp, pp)

TESTCROSS

• TO DETERMINE WHETHER AN ORGANISM WITH A DOMINANT PHENOTYPE (PURPLE FLOWERS) IS HOMOZYGOUS DOMINANT OR HETEROZYGOUS

• TESTCROSS = THE BREEDING OF AN ORGANISM OF UNKNOWN GENOTYPE WITH A HOMOZYGOUS RECESSIVE

TESTCROSS

GENOTYPE V. PHENOTYPE

LAW OF INDEPENDENT ASSORTMENT

• EACH PAIR OF ALLELES SEGREGATES INTO GAMETES INDEPENDENTLY

• DIHYBRID CROSS = TESTING MORE THAN ONE TYPE OF GENE AT A TIME

• DIHYBRID CROSS FUNDAMENTAL TO MENDEL’S LAW OF INDEPENDENT ASSORTMENT

PUNNETT SQUARES

• YOU NEED TO BE ABLE TO COMPLETE 3 TYPES OF PUNNETT SQUARES:– MONOHYBRID– DIHYBRID– TRIHYBRID

RULES OF PROBABILITY

• RULE OF MULTIPLICATION = THE PROBABILITY THAT INDEPENDENT EVENTS WILL OCCUR SIMULTANEOUSLY IS THE PRODUCT OF THEIR INDIVIDUAL PROBABLITIES

• RULE OF ADDITION = THE PROBABILITY OF AN EVENT THAT CAN OCCUR IN TWO OR MORE INDEPENDENT WAYS IS THE SUM OF THE SEPARATE PROBABILITIES OF THE DIFFERENT WAYS

SEGREGATION OF ALLELES IS CHANCE

PRACTICE YOUR PUNNETT SQUARES

IN CLASS PROBLEMS

INCOMPLETE DOMINANCE

• ONE ALLELE IS NOT COMPLETELY DOMINANT OVER THE OTHER, SO THE HETEROZYGOTE HAS A PHENOTYPE THAT IS INTERMEDIATE BETWEEN THE PHENOTYPES OF THE TWO HOMOZYGOTES

INCOMPLETE DOMINANCE

CODOMINANCE• INHERITANCE WHERE THERE IS FULL

EXPRESSION OF BOTH ALLELES IN THE HETEROZYGOTE

• EXAMPLE: MN BLOOD-GROUP LOCUS CODES FOR THE PRODUCTION OF SURFACE PROTEINS ON THE RBC. THERE ARE 3 BLOOD TYPES: M (MM), N(NN), AND MN– THE MN BLOOD TYPE IS THE RESULT OF FULL

PHENOTYPIC EXPRESSION OF BOTH ALLELES IN THE HETEROZYGOTE; BOTH MOLECULES, M AND N, ARE PRODUCED ON THE RBC

TAY-SACHS• AN EXAMPLE OF A DISEASE CAUSED BY

CODOMINANCE• BRAIN CELLS OF TAY-SACHS BABIES LACK A

CRUCIAL LIPID-METABOLIZING ENZYME. LIPIDS BUILD UP IN BRAIN AND LEADS TO DEATH

• THE NORMAL ALLELE AND TAY-SACHS ALLEL ARE CODOMINANT. HETEROZYGOTES PRODUCE EQUAL NUMBERS OF NORMAL AND BAD GENES.

• THEY LACK DISEASE SYMPTOMS BECAUSE BRAIN CAN COPE WITH HALF

THE NORMAL AMOUNT OF ENZYME

MULTIPLE ALLELES

• SOME GENES MAY HAVE MULTIPLE ALLELES, MORE THAN JUST TWO FORMS OF A GENE.

• THE INHERITANCE OF THE ABO BLOOD GROUP IS AN EXAMPLE OF A LOCUS WITH THREE ALLELES

• THERE ARE FOUR POSSIBLE PHENOTYPES: A, B, AB, O

MULTIPLE ALLELES FOR BLOOD TYPE

BLOOD TYPING

• ALLELES IA AND IB ARE CODOMINANT, SINCE BOTH ARE EXPRESSED IN HETERO.

• ALLELES IA AND IB ARE DOMINANT TO ALLELE i, WHICH IS RECESSIVE

• *** FOR A BLOOD TRANSFUSION TO BE SUCCESSFUL, THE RED BLOOD CELL ANTIGENS OF THE DONOR MUST BE COMPATIBLE WITH THE ANTIBODIES OF THE RECIPIENT

• TYPE O IS “UNIVERSAL DONAR”

PLEIOTROPY• THE ABILITY OF A SINGLE GENE TO HAVE

MULTIPLE PHENOTYPIC EFFECTS• THERE ARE MANY HEREDITARY DISEASES

IN WHICH A SINGLE DEFECTIVE GENE CAUSES COMPLEX SET OF SYMPTOMS (SICKLE CELL)

• ONE GENE CAN ALSO INFLUENCE A COMBO OF UNRELATED CHARACTERISTICS. IN CATS, THE GENE THAT CONTROLS FUR PIGMENT ALSO INFLUNCES CONNECTIONS BTW. EYES AND BRAIN. A DEFECTIVE GENE CAUSES BOTH ABNORMAL PIGMENTATION AND CROSS-EYE CONDITION

EPISTASIS• INTERACTION BETWEEN TWO

NONALLELIC GENES IN WHICH ONE CHANGES THE PHENOTYPIC EXPRESSION OF THE OTHER

• IF ONE GENE SUPPRESSES THE PHENOTYPIC EXPRESSION OF ANOTHER, THE FIRST GENE IS SAID TO BE EPISTATIC TO THE SECOND

• IF EPISTASIS OCCURS BETWEEN TWO NONALLELIC GENES, THE PHENOTYPIC RATIO IN A DIHYBRID WILL DEVIATE FROM THE 9:3:3:1 RATIO

EPISTASIS

ALL OFFSPRING WITH cc ARE WHITE, REGARDLESS OF THEGENOTYPE FOR THE BLACK/BROWN GENETIC LOCUS

POLYGENIC INHERITANCE

• MODE OF INHERITANCE IN WHICH THE ADDITIVE EFFECT OF TWO OR MORE GENES DETERMINES A SINGLE PHENOTYPIC CHARACTER

• EXAMPLE: SKIN PIGMENT IN HUMANS IS CONTROLLED BY AT LEAST 3 SEPARATELY INHERITED GENES

POLYGENIC INHERITANCE

A BLENDING EFFECT IS THE BASIC IDEA-INCOMPLETE DOMINANCE

PEDIGREE ANALYSIS

• A FAMILY T REE THAT DIAGRAMS THE RELATIONSHIPS AMONG PARENTS AND CHILDREN ACROSS GENERATIONS AND SHOWS THE INHERITANCE PATTERN OF A PARTICULAR PHENOTYPE.– SQUARES SYMBOLICE MALES, CIRCLES

FEMALES– HORIZONTAL LINE CONNECTING MALE AND

FEMALE INDICATES MATING– SHADED SYMBOL REPRESENTS TRAIT BEING

TRACED

PEDIGREE

• CAN BE USED FOR:– DETERMINING IF A TRAIT IS RECESSIVE OR

DOMINANT– PREDICTING THE OCCURRENCE OF A TRAIT IN

FUTURE GENERATIONS, AS IN PUNNETTS– Example: PROBABILITY OF WIDOW’S PEAK?

» (DOMINANT ALLELE)

MATING Ww X Ww

--PROBABILITY OF WW = 1/4

--PROBABILITY OF Ww = 2/4

--PROBABILITY OF WIDOW’S PEAK = 3/4

(RULE OF ADDITION)

RECESSIVELY INHERITED DISORDERS

• RECESSIVE ALLELES THAT CAUSE HUMAN DISORDERS ARE USUALLY DEFECTIVE VERSIONS OF NORMAL ALLELES– THE PHENOTYPES ARE EXPRESSED ONLY IN

HOMOZYGOTES– HETEROZYGOTES ARE CARRIERS, AND CAN

PASS ON THE TRAIT– MOST PEOPLE WITH RECESSIVE DISORDERS

ARE BORN TO NORMAL CARRIER PARENTS

CYSTIC FIBROSIS

• THE MOST COMMON LETHAL GENETIC DISEASE IN U.S.– STRIKES 1/2500 CAUCASIANS– 4% OF CAUCASIANS ARE CARRIERS– DOMINANT ALLELE CODES FOR A MEMBRANE

PROTEIN THAT CONTROLS CHLORIDE TRAFFIC. CHLORIDE CHANNELS ARE DEFECTIVE OR ABSENT IN PEOPLE WITH DISEASE

– DISEASE SYMPTOMS RESULT FROM THE ACCUMULATION OF MUCUS IN PANCREAS, INTESTINES, AND LUNGS

TAY-SACHS

• OCCURS IN 1/3600 BIRTHS

• 100 TIMES HIGHER INCIDENCE IN CENTRAL EUROPEAN MEDITERRANEAN JEWS– BRAIN CELLS OF BABIES ARE UNABLE TO

METABOLIZE GANGLIOSIDES (A LIPID), BECAUSE AN ENZYME DOES NOT FUNCTION

– LIPIDS BUILD UP IN BRAIN, CAUSING SEIZURES, BLINDNESS AND DENGENERATION OF MOTOR AND MENTAL ABILITIES. DEATH USUALLY OCCURS IN A FEW YEARS

SICKLE CELL ANEMIA• THE MOST COMMON INHERITED DIEASE

AMONG AFRICAN AMERICANS• AFFECTS 1/400 AFRO AMERICANS BORN IN U.S.

– CAUSED BY A SINGLE AMINO ACID SUBSTITUTION IN HEMOGLOBIN

– ABNORMAL HEMOGLOBIN MOLECULES LINK TOGETHER AND CLUMP. RBC’S DEFORM FROM NORMAL TO SICKLE-SHAPE

– HETEROZYGOTES ARE RESISTANT TO MALARIA, WHICH IS WHY THERE IS A HIGH RATE OF HETERZYGOSITY IN AFRICA

CONSANGUINITY

• A GENETIC RELATIIONSHIP THAT RESULTS FROM SHARED ANCESTRY– THE MORE CLOSELY RELATED THE

PARTNERS, THE HIGHER INCIDENCE OF INHERITIED DISEASES IN OFFSPRING

– MOST CULTURES FORBID MARRIAGE BETWEEN CLOSELY RELATED ADULTS BECAUSE OF THIS

DOMINANTLY INHERITED DISORDERS

• LETHAL DOMINANT ALLELES ARE MUCH RARER THAN LETHAL RECESSIVES BECAUSE THEY:– ARE ALWAYS EXPRESSED, EFFECTS

NOT MASKED IN HETEROZYGOTES– USUALLY RESULT FROM NEW GENETIC

MUTATIONS THAT OCCUR IN GAMETES AND LATER KILL THE EMBRYO

HUNTINGTON’S DISEASE

• A DEGENERATIVE DISEASE OF THE N.S., IS CAUSED BY A LATE-ACTING LETHAL DOMINANT ALLELE.

• PHENOTYPIC EFFECTS DO NOT APPEAR UNTIL AGE 35-40

• MOLECULAR GENETICISTS HAVE LOCATED THE GENE NEAR THE TIP OF CHROMOSOME #4

MULTIFACTORIAL DISORDERS

• DISEASES THAT HAVE BOTH GENETIC AND ENVIRONMENTAL INFLUENCES– HEART DISEASE, DIABETES, CANCER,

ALCOHOLISM, SOME MENTAL ILLNESSES

GENETIC COUNSELING

• HELPS PARENTS ACCESS THE RISK OF PASSING ON DISORDERS

• RISK ASSESSMENT INCLUDES STUDYING FAMILY HISTORY USING MENDEL’S LAW OF SEGREGATION TO DEDUCE THE RISK

CARRIER RECOGNITION

• SEVERAL TESTS ARE AVAILABLE TO DETERMINE IF PROSPECTIVE PARENTS ARE CARRIERS OF GENETIC DISORDERS

– TESTS CURRENTLY AVAILABLE CAN DETERMINE CARRIERS FOR TAY-SACHS, C.F., AND SICLE-CELL

– TESTS ENABLE PEOPLE TO MAKE INFORMED PARENTING DECISIOINS

FETAL TESTING• PARENT CARRIERS CAN TEST EMBRYO

• AMNIOCENTESIS-AMNIOTIC FLUID CAN BE TESTED FOR DISORDERS (WEEK 14-16)

• CHORIONIC VILLUS SAMPLING (CVS)- SUCTION OFF SMALL AMT. OF FETAL TISSUE FROM CHORIONIC VILLI OF PLACENTA. CELLS CAN BE KARYOTYPED AND ASSESSED FOR DISORDERS (WEEK 8-10)

FETAL TESTING

NEWBORN SCREENING

• IN MOST U.S. HOSPITALS, TESTS ARE PERFORMED AT BIRTH TO DETECT DISORDER SUCH AS PHENYLKETONURIA (PKU), A DISEASE CHARACTERIZED BY THE INABILITY TO METABOLIZE THE AMINO ACID PHENYLALANINE (FOUND IN NUTRASWEET) AND THE BUILD UP OF THIS A.A. CAUSES MENTAL RETARDATION.