Chapter 6 1 Principles of Inheritance retardation a Congenital disorders present at birth genetic environmental causes mental b Congenital malformations structural defects due to errors in fetal development mostly genetic causes brain malformation Inherited genetic disorders that appear in later life are not considered congenital c 2 Principles of Inheritance from parent to offspring a Gregor Mendel first to notice that traits are transmitted in a predictable manner b Phenotype observable physical biochemical traits eye color c Genotype unique genetic makeup results from 23 maternal and 23 paternal chromosomes uniting at conception XX XY d Chromatids two identical linear chromosome units which separate during meiosis e Centromere point at the center of X where 2 sister chromatids fuse f Diploid human chromosomes exist in homologous pairs with unique DNA sequences one chromosome from each parent i 23 pairs 46 chromosomes 3 Principles of Inheritance a Electron micrograph of chromosome two sister chromatids attached at centromere i P short arm ii Q long arm b Standard map of banding pattern of each of the 23 human chromosomes i Alleles 4 Principles of Inheritance a Chromosomes characterized by i Total size ii X arm lengths iii Specific band patterns when exposed to certain stains 5 23 pairs of chromosomes a 22 homologous pairs autosomes b 1 hemizygous pair sex chromosomes i Female XX homologous 1 X from each parent ii Male XY heterogeneous 1 maternal X and 1 paternal Y 6 Principles of Inheritance a Meiosis Replication of sex chromosome b Mitosis replication of autosomes c Female puberty mitosis 2 producing eggs d Two germ cells egg and sperm each with haploid number of chromosomes combine to form new cell with complete 46 chromosomes e Requires two divisions of chromosome DNA 7 Principles of Inheritance a Stages of Meiosis 8 Principles of Inheritance a Genetic Traits i Duplicated sister chromatids closely contact their homologous pairs ii Crossing over parts of homologous pairs are precisely exchanged in order to mix maternal and paternal genes results in new genetic combination iii First cell division 2 3 cross over events creates 2 diploid cells iv Second cell division sister chromatids pulled apart creates 4 haploid cells i Genes coding for specific trait are found at specific loci on a chromosome and come in several forms called alleles ii Each gene has 2 alleles 1 from each parent and can determine homozygous heterozygous traits b Types of alleles dominant and recessive must be homozygous to be expressive c Types of traits i Codominant no clear dominant recessive alleles traits combine ii Monogenic interaction of single gene locus iii Polygenic interaction of multiple gene loci heritable unpredictable affected by environmental factors 9 Principles of Inheritance a DNA mutation and repair i Mutation rare permanent change in DNA structure ii Mutagens radiation chemicals viruses etc iii Types of DNA damage 1 Single stranded break easy repair complementary strand still present 2 Double stranded break permanent loss of genetic information at break point possible iv Epstein Barr Virus 1 Cause lymphomas 2 Nasal pharyngeal carcinomas 10 Principles of Inheritance a DNA mutation types b Point mutation single base pair substitution results in affected codon to code an abnormal amino acid c Frameshift mutation addition removal of 1 or more bases change reading frame all codons change downstream of mutation dramatic change to amino acid sequence Everything shifted and changed abnormal i All amino acids will be different 11 Principles of Inheritance a Genetic Disorders i Apparent at birth or later in life ii iii Classified as Inherited or acquired during fetal development 1 Mendelian single gene disorders DNA mutation coding for particular protein 2 Chromosomal abberations segment loss gain translocation 3 Multifactorial Polygenic disorders 4 Non Mendelian single gene disorders triple repeat mutations mitochondrial gene mutations genomic imprinting mutations 12 Mendelian Single Gene Disorders a Alteration or mutation of single gene b Defective gene codes for abnormal enzymes and proteins c Classification i Location of defective gene autosomal sex chromosome d Mode of transmission dominant recessive e Pedigree charts tool to determine pattern of inheritance 13 Chromosomal Abnormalities a Abnormal number of chromosomes or altered chromosome structure due to errors in chromosome separation or crossing over during meiosis mitosis b Etiological factors idiopathic radiation chemicals viruses c Risk factors advanced maternal downs syndrome or paternal age achondroplasia dwarfism torso is normal slightly enlarged or normal head very short limbs abnormalities in parental chromosome structure d Mutations gametes telomere affected easily damaged e Risk starts at 30 by age 35 risk is 1 in 500 14 Chromosomal Abnormalities a Aneuploidy ploid of chromosomes i Abnormal chromosome number more less than 46 ii Nondisjunction paired homologous pairs fail to separate resulting germ cells have 22 and 24 chromosomes each when combined with normal haploid gametes the fertilized cell has 45 or 47 chromosomes iii Anaphase lag one chromosome left out of newly formed cell nucleus one daughter cell normal and one with a deficiency of 1 chromosome monosomy incompatible with life less than or equal to 1 iv Polysomy daughter cell with excess chromosomes viable fetus possible severe disability greater than 2 1 That s why downs syndrome affected fetuses can still be born 15 Chromosomal Abnormalities a Abnormal chromosome structure i Breakage and loss rearrangement of chromosome pieces 1 Meiosis crossing over errors portions of chromosome lost deletions or attached upside down inversion or attached to wrong chromosome translocation 2 Mitosis 16 Chromosomal Abnormalities a Abnormal chromosome structure i Translocation 1 DNA exchanged between nonhomologous chromosome 2 Reciprocal no lost genetic material increased risk of producing abnormal gametes 3 Robertsonian exchange one long chromatid arm for a short one Isochromosomes sister chromatids separate incorrectly at centromere ii 17 Chromosomal Abnormalities a Abnormal chromosome structure i Inversion 1 Chromosome section removal and upside down reinsertion 2 No net loss gain of genetic material 3 No consequence to carrier but results in cross over mutations of offspring ii Deletion 1 Break in arm of single chromosome results in DNA fragment without centromere causing piece