BO101 Molecular Genetics Lecture 3 PDF

Mendelian Genetics and Chromosomes BO101 - Molecular Genetics - Lecture 3 Dr Andrew Flaus, Biochemistry Mendelian genetics Mendel and crossing of pea plants ๏ Gametes ‣ Cell with only 1 of each chromosome type ‣ Gametes produced Carpels: female, ovules Stamens: male...

Mendelian Genetics and Chromosomes BO101 - Molecular Genetics - Lecture 3 Dr Andrew Flaus, Biochemistry Mendelian genetics Mendel and crossing of pea plants ๏ Gametes ‣ Cell with only 1 of each chromosome type ‣ Gametes produced Carpels: female, ovules Stamens: male, pollen ๏ Crossing = fertilisation ‣ Crossing of parent plants, P Cross-pollinate by manual transfer of pollen ‣ Filial generation, F1 Diploid plant arising from cross Campbell g 14.2 fi Mendel’s monohybrid crosses ๏ Character ‣ Genetically encoded feature Example: Flower colour ๏ Trait ‣ Particular version of a character Example: Purple or white owers Campbell g 14.3 fi fl Mendel’s monohybrid crosses 1. Cross parental plants (P) 2. Observe F1 generation ‣ One characteristic dominates 3. F2 from self-crossing of F1 ‣ Count ratio of traits Campbell g 14.3 fi Mendel’s monohybrid crosses 1. Cross parental plants (P) ‣ Compare traits for a character 2. Observe F1 generation ‣ One characteristic dominates 3. F2 from self-crossing of F1 ‣ Count ratio of traits ๏ Observe trait ratio ~3:1 Campbell table 14.1 Mendel’s hypotheses 1. Alternative gene versions can explain character variations ‣ Alleles = alternative versions of gene 2. An organism inherits 2 alleles, one from each parent ‣ Homozygous = identical alleles, heterozygous = different alleles 3. Gametes carrying alleles are separated ‣ Law of Segregation: The two alleles for a heritable character segregate during gamete formation and end up in different gametes 4. One allele can prevail over another ‣ Dominant alleles prevail over recessive alleles Campbell p327-328 1. Law of Segregation ๏ Law of Segregation ‣ Two alleles for a heritable character segregate during gamete formation and end up in different gametes ๏ Punnett square ‣ Diagram for predicting allele combinations ‣ Large letter indicates dominant allele ๏ Genotype and phenotype differ ‣ Genetic makeup may be masked in observable character Campbell g 14.5 fi Genotype v phenotype ๏ Law of Segregation ‣ Two alleles for a heritable character segregate during gamete formation and end up in different gametes ๏ Phenotype ‣ Observable traits of an organism ๏ Genotype v phenotype ‣ Genetic makeup may be masked in observable traits Campbell g 14.6 fi 2. Law of Independent Assortment ๏ Dihybrid cross ‣ Crossing of two characters at same time yellow/green v round/wrinkled ‣ Observe that F2 is mix of all possible combinations ๏ Law of Independent Assortment ‣ Two or more genes segregate independently of each other during gamete formation Campbell g 14.8 fi Summary of Mendel’s Laws 1. Law of Segregation ‣ Two alleles for a heritable character segregate during gamete formation and end up in different gametes 2. Law of Independent Assortment ‣ Two or more genes segregate independently of each other during gamete formation ๏ Dominance ‣ One allele prevails over others Campbell gs 14.5, 14.8 fi More complex cases of inheritance A. Incomplete dominance ๏ Complete dominance ‣ Mendel’s simplest result ‣ F1 has phenotype of one of P traits ๏ Incomplete dominance ‣ F1 has phenotype intermediate between parental traits ‣ F2 has 1:2:1 phenotype ratio Heterozygote has intermediate character Campbell g 14.10 fi B. Pleiotropy, polygenic inheritance, nurture ๏ Pleiotropy ‣ A single gene has multiple effects on organism Example: Sickle cell disease leads to multiple health issues ๏ Polygenic inheritance ‣ Multiple genes combine to decide overall phenotype Example: Skin colour ๏ Nature v nurture ‣ Environment affects phenotype ‣ Example: Skin colour and tanning Campbell g 14.13 fi C. Multiple alleles ๏ Multiple alleles ‣ More than 2 genotypes possible ‣ Different combinations of alleles can have multiple outcomes ‣ Example: ABO blood groups Alleles A, B or none Phenotypes A, B, AB or O (none) Campbell g 14.11 fi D. Epistasis ๏ Epistasis ‣ Gene at one locus affects gene at another locus ๏ Example: Labrador colour ‣ Genotype of E affects B EE/Ee Chocolate BB/Bb Black White EE/Ee Chocolate bb ? (Golden) ee ? BB/Bb/bb ? D. Epistasis ๏ Epistasis ‣ Gene at one locus affects gene at another locus ๏ Example: Labrador colour ‣ Gene for colour black v brown (B,b) Black is dominant (BB,Bb) Brown is recessive (bb) ‣ Gene for colour deposition (E,e) Observing colour is dominant (EE,Ee) Not observing colour is recessive (ee) No colour = cream/yellow coat, irrespective of genotype for B,b Campbell g 14.12 fi Genetic linkage and chromosomes Alleles are DNA sequences on chromosomes Campbell g 14.4 fi Chromosomal basis for Mendel’s laws ๏ Law of segregation ‣ Alleles for a gene are on homologous chromosomes ‣ Alleles separate into different gametes ๏ Law of independent assortment ‣ Alleles for genes on non– homologous chromosomes are independent ‣ Alleles assort independently Campbell g 15.4 fi Genes on homologous chromosomes ๏ Linked genes ‣ Genes located nearby on same chromosome ‣ Tend to be inherited together ๏ Linkage is imperfect ‣ Dilutes with distance between genes along chromosome expected by linkage unexpected Campbell g 15.10 fi Chromosomal basis of linkage ๏ TH Morgan and fruit ies ‣ Used fruit ies as model organism ‣ Wrote important textbook in 1915 “Mechanism of Mendelian Heredity” ๏ Crossover ‣ Genes on same chromosome should have complete linkage ‣ Crossovers can occur in meiosis at F1 generation crossover ‣ Alleles swap between homologous chromosome pairs Linkage is broken Campbell g 15.10 fi fl fl Linkage map reveals gene location ๏ Recombination frequency ‣ Loss of linkage as percentage Measure by dihybrid crosses ๏ Linkage map ‣ Based on mutual recombination frequency of many genes ‣ Calculate relative location of genes along chromosome Used for original genome assembly ‣ Order is same as gene position in DNA sequence Easier (and cheaper) to sequence genome nowdays! Campbell g 15.11, 15.12 fi Human genetic diseases Human traits and Mendelian inheritance ๏ Pedigree analysis ‣ Impossible to perform human matings! ‣ Use retrospective family history ‣ Standardised symbolic code Campbell g 14.15b fi Human traits and Mendelian inheritance ๏ Pedigree analysis ๏ Recessive disorders ‣ Example: Albinism ‣ Allele frequencies may vary in different sub-populations ‣ Disease-causing recessive alleles are rare due to selection Risk elevated for consanguineous matings (close relatives) Debate: Some geneticists argue deleterious phenotypes abort at embryo stage, reducing risks Campbell g 14.16 fi Human traits and Mendelian inheritance ๏ Pedigree analysis ๏ Recessive disorders ๏ Dominant disorders ‣ Example: Achondroplasia Dwar sm by limb shortening ‣ Disease-causing dominant alleles are rare Exceptions are late-onset diseases Example: Huntington’s disease Campbell g 14.18 fi fi Chromosomal non-disjunction ๏ Non-disjunction ‣ Chromosomes not moving apart correctly in meiosis I or II ‣ Results in gametes with -1 or +1 chromosome Campbell g 15.13 fi Chromosomal non-disjunction ๏ Non-disjunction ‣ Results in gametes with -1 or +1 chromosome ๏ Aneuploidy ‣ Diploid cell with abnormal number of one chromosome 10-25% human conceptions Usually lethal ‣ Monosomic: 1 homologue ‣ Trisomic: 3 homologues Campbell g 15.13 fi Aneuploidy and disease ๏ Non-disjunction ๏ Aneuploidy ‣ Trisomy: 3 homologues (2+1) ๏ Down syndrome ‣ Trisomy 21 ‣ ~1 in 546 live births in Ireland ‣ Linked with maternal age Seems to be tolerated for shorter chromosomes, with less genes? Campbell g 15.15 fi Summary of lecture ๏ Mendel’s laws ‣ Law of segregation ‣ Law of independent assortment ‣ Chromosomal basis of laws ๏ More complex inheritance ๏ Genetic linkage ๏ Human genetic diseases ‣ Mendelian traits ‣ Non-disjunction and aneuploidy Learning outcomes for lecture ๏ On successful completion of this lecture, you will be able to: ‣ Describe Mendel’s laws of segregation and independent assortment using examples ‣ Explain how complex inheritance patterns results from dominance, epistasis, pleiotropy and polygenic inheritance ‣ Use examples of human genetics to illustrate Mendelian inheritance, and the implications this has for medical diagnosis and treatment ‣ Explain the relationship between genes and chromosomes ‣ Describe how genetic linkage affects inheritance ‣ Explain how alterations in chromosome number and structure can lead to human genetic disorders