Human Genetics & Evolution
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  • 1. Yapa Wijeratne Human Genetics Allele- alternative forms of a gene, which occur at the same locus on homologous chromosomes.(If the maternal & paternal alleles are identical, person is homologous ) Dominant allele- an allele that exerts its phenotypic effect in the heterozygous; it hides the expression of the recessive allele. Recessive allele- an allele that exerts its phenotypic effect only in the homozygous; its expression is masked by a dominant allele. Gene locus- the specific location of a particular gene on homologous chromosomes. Genotype- the genes of an organism for a particular trait or traits; e.g. BB , Aa Phenotype- the visible expression of a genotype. e.g. brown eyes, attached earlobes Heterozygous- possessing unlike alleles for a particular trait. Homozygous- possessing 2 identical alleles for a particular trait. Autosome- any chromosome other than a sex chromosome. Mutation- an alteration in chromosome structure or number & also an alteration in a gene due to a change in DNA composition. Polyploidy (polyploid)- a condition in which an organism has more than 2 complete sets of chromosomes. Sex chromosome- a chromosome that determines the sex of an individual ; in animals, females have 2 X chromosomes & males have an X & Y chromosome. X-linked gene- gene located on the X chromosomes that does not control a sexual feature of the organism. Karyotype- chromosomes arranged by pairs according to their size, shape & general appearance in mitotic metaphase. Nondisjunction- the failure of homologous chromosomes or daughter chromosomes to separate during meiosis I & meiosis II respectively. Anticodon-3 nucleotides on a tRNA molecule attached to a complementary codon on mRNA. Codon- 3 nucleotides of DNA or RNA; it codes for a particular AA or termination of translation. Exon- in a gene, the portion of the DNA code that is expressed as the result of polypeptide formation. Intron- non-coding segment of DNA that are transcribed but removed before mRNA leaves the nucleus. Transcription- the process whereby a DNA strand serves as a template for the formation of mRNA. Translation- the process whereby the sequence of codons in mRNA determines (is translated into) the sequence of AAs in a polypeptide. Double helix of DNA- maintain stability of structure. DNA contains the information needed to encode proteins. 64 combinations are possible within 4 bases (20 AA). 3 bases represent a 1 AA. Most proteins have more than one complementary codon.-Redundancy of AA. Gene- sequence of DNA which codes for one polypeptide. 1
  • 2. Yapa Wijeratne Replacing / removal/ addition of nucleotides may lead to mutations. If the replaced AA has same chemical properties of the previous AA the resulting protein may function normally. Replacing may sometimes lead to enhance the function of a protein. Polymorphism Difference in DNA sequence among individuals, groups or populations that gives rise to different forms. e.g. blood group formation. Producing a protein or a characteristic of the organism (trait) is the expression of a gene. In the heterozygous state the dominant allele (dominant trait) expresses itself while the recessive allele (recessive trait) does not. House keeping genes are the genes which produce structurally & functionally vital proteins for the normal integrity of a cell. Mutations of these genes will produce proteins which are not capable of doing particular functions. 75% of the genes can not afford even a subtle change in their structure. (sequence of AA) Miscarriages – (Abortions- particularly within 1st 3 months of pregnancy) will result, if mutations occur in house keeping genes. Other 25% of genes (polymorphic genes) can afford subtle mutations but it may reduce or enhance its expression. Gene pool- all the genetic material in a given population. If a gene has a frequency over 1% in a gene pool, that variant of the gene is accepted as a polymorphic form of that particular gene. Polymorphic forms of a morphogene give rise to morphological variations of individual species. Variations are vital to withstand environmental changes. e.g. Defective Hb (sickle cell) prevents African people from infecting with malaria. Having sickle cell Hb is now vital for the continuity of African people. Heterozygous advantage - In the heterozygous state if the recessive gene is defective, it is covered by the normal gene which is dominant. In Heterozygous state both dominant & recessive genes are expressed but dom. gene overrides. There are various mechanisms to prevent the expression of certain genes. e.g. Attaching to the nuclear membrane but still a small portion of the inactivated X chromosome [Barr body] is necessary for the secondary sexual characteristics of a female. So having a 1X chromosome will result defects. This inactivation is the reason for the females to become carriers of various chromosomal abnormalities. Genetic load-amount of hidden inactive lethal mutations. There is a high chance of these genes to express in marriages between relatives. That is why 1st cousin marriages are discouraged. Chromosomes Centromere is an adenine-thymine (A-T) rich region ranging in size from 10 2-106 base pairs. It binds several proteins with high affinity. This complex- Kinetochore provides an anchor for the mitotic spindle. 2
  • 3. Yapa Wijeratne The ends of each chromosome contain structures -> Telomeres Telomeres consist of short, repeat TG-rich sequences. Proteins. Telomeres prevent joining free 3’-->5’ ends of DNA strand. DNA in eukaryotic genome unique/ non-repetitive sequence repetitive sequence moderately repetitive highly repetitive Repetitive sequence is found in telomeres. Telomerase – is the enzyme responsible for telomere synthesis & thus for maintaining the length of the telomere. After each division telomere shortening Aging(when telomere cannot loss, sequence stops) Malignant transformation Cancer cells do not depend on telomeric sequence. Telomerase restores/ replaces lost parts, telomeric sequence. So cell division doesn’t stop. So Cancer chemotherapy Drug development Telomerase The basic number of chromosomes in the somatic cells of an individual or a species- Somatic number- is designated 2n. 2n --> homologous chromosomes for each given chromosomes. Karyotype Characteristic chromosome complement of a eukaryotic species. The preparation & study of Karyotype is part of cytogenetics - Karyotype analysis. Human Karyotype preparation 1. Blood cells are centrifuged. WBC & RBC are separated. 2. Induce the cells to divide.-chemicals 3. Colchicine is added to stop division of WBC.-to arrest the division in metaphase (usually 48-72 hrs after begin) 4. Break he nuclear membrane. 5. Hanging drop method- to divide each cell’s nuclear material. 6. Slide is prepared. Sample is fixed & stained (Giemsa, immunofluorecent stains). 7. Slide is examined for cells about to divide. 8. Chromosomes are photographed, enlarged & then cut apart. Position of centromere Banding appearance can identify homologous chromosomes. Reverse banding appearance -> different banding pattern -> but same areas can be identified. Metacentric chromosomes- centromeres in the middle. Submetacentric chromosomes- centromeres intermediate position/ towards the end. Acrocentric chromosomes- centromeres close to one end /end. Chromosomal aberrations 1.Numerical Polyploidy Aneuploidy-missing or having an extra chromosome. Monosomies or trisomies 3
  • 4. Yapa Wijeratne Remove 1 chromosome for certain chromosomes. Loss or extra chromosome-if in germ cells, not compatible for life. definitely cause problem (brain development & morphology) ->syndromes e.g. monosomic for <number> chromosome Syndrome Sex Chromosomes Down M/F Trisomy 21 Patau M/F Trisomy 13 Edward M/F Trisomy 18 Turner F XO Metafemale F XXX (or XXXX) Klinefelter M XXY (or XXXY) XYY M XYY O-sex chromosome is missing. Nondisjunction-occurs when either homologous fail to separate during anaphase I of meiosis Or sister chromatids fail to separate during anaphase II. Can happen when people are old as many cells are not functioning properly. Nondisjunction is more common during meiosis I than during meiosis II. It can also occur during mitosis. In animals , autosomal monosomies & trisomies are generally lethal. e.g. Down syndrome o Aneuploidy situation o Alter morphological & IQ o Space between eyes is large o lowstep ears Klinefelter-aberrations in sex chromosome-usually IQ is OK. 2.Structural Chromosomal mutations 1. Inversion 2. Translocation 3. Deletion 4. Duplication Inversion When a segment of a chromosome is turned around 180 0. New position might lead to altered gene activity. Translocation Movement of a chromosomal segment from one chromosome to another, non- homologous chromosome. Usually have reduced fertility due to production of abnormal gametes. When translocations occur Down syndrome->Translocation Down syndrome 2 types. i. Reciprocal- heterologous chromosomes ii.Robertsonian Deletion When an end of a chromosome breaks off or when two simultaneous breaks lead to the loss of a segment. e.g. cat’s cry syndrome small head mentally retarded facial abnormalities abnormal development of the glottis & larynx 4
  • 5. Yapa Wijeratne Duplication Doubling of a chromosomal segment. Fragile X syndrome Isochromosomes Ringchromosomes Gene mutations 1.Frame shift mutations Drastic. 1 or more nucleotides are inserted or deleted from DNA. Then “reading frame” shifts & sequence of codons is altered. 2.Point mutations A change in a single nucleotide & therefore a change in a specific codon. When one base is substituted for another, the results can be variable. Can be drastic. e.g. Tyr codon Additional Tyr codon Stop codon His codon Normal protein Incomplete protein Faulty protein Silent mutation Nonsense mutation Missense mutation 3.Mosaicism Chromosomal aberrations 1. Numerical a. Polyploidy b. Aneuploidy c. Monosomies or trisomies 2. Structural a. Chromosomal mutations i. Inversion ii. Translocation iii. Deletion iv. Duplication b. Gene mutations i. Frame shift mutations ii. Point mutations 3. Mosaicism 5
  • 6. Yapa Wijeratne Human Evolution Primates ( chimpanzees, orangutan, gorilla, human) One cell tube birds bat (Unicellular) (coelenterate) amphibians Primates-most of them are mammals 4 legged 2 legged Homo erectus Homo sapiens Changes in vertebral column 4 legged -> brain & spinal cord in one plane 2 legged -> Angulation between brain & spinal cord Skull Cranium (Cranial cavity) small Brain is small Increase in the size of Cranial cavity Sagittal crest (top of the skull) -> for prominent muscle attachment ( in low primates) No Sagittal crest -> in Homo erectus & Homo sapiens Supra ciliary ridges(eye brows area) prominent in low primates. Vision- position of eye- binocular vision is absent in lower animal Facial skeleton- long snout –jaws show Prognathism – because nasal cavity is large Humans -> Prognathism is absent Teeth – lower animals 1. Herbivore-leaves/vegetarian diet-more prominent grinding teeth-Molar teeth 2. Carnivore-meat eating-Canine (means “dog”) sharpness is reduced. 3. Omnivore-both Hand- prominent & opposable thumb Legs- mobility of the big toe is reduced. 6