| What is a mutation? | Permanent alteration of any part of DNA sequence |
| How are mutations classified? | Spontaneous ( appear for no known reason, result from biological and chemical processes, during enzymatic process.)
Non-Spontaneous (Influenced by an external factor, Induced by natural or artificial factor called mutagen) |
| Give examples on induced mutations. | UV radiation usage or industrial pollutants and X-rays. (higher frequency than spontaneous ones) |
| Where are the possible places that would undergo mutation? | Somatic mutations (any cell except germs, transmitted by mitosis, may lead to altered functionality and tumors- Golden color of red apples)
Germinal mutations (greater in significance since transmitted as gametes, potential of being expressed, basis of genetic diversity and evolution)
Can be benificial, neutral or harmful |
| How are mutations classified based on type of molecular change? | Gene mutations and Genomic mutations. |
| Talk about gene mutations. | Alteration in nucleotide sequence of DNA molecule or gene.
may be substitution (change in base pair know as point mutation, AKA if prymidine replaces prymidine or purine replaces purine it is called transition. If purine replaces prymidine or vice versa called transversion.
Insertion or deletion. |
| What are the types of gene mutations? | Silent ( No change in amino acid)
Missense (change in one amino acid)
Nonsense (change into nonsense codon)
Frameshift (Altering in reading frame of translation, addition or deletion of any nucleotide sequence except multiples of 3, with possibility of having stop codons) |
| Talk about the metabolic diseases caused by the gene mutation. | Due to enzyme gene mutation. Example (phenylketonuria PKU result in mental retardation, seizured, behavorial problems, autosomal recessive allele, inability to convert digested amino acid phenylalanin into tyrosine, whom differs by OH group. This reaction is catalyzed by phenylalanine hydroxylase, PKU is a mutation in this enzymes gene, which leads to phenylalanine over dosage which leads to toxicity. |
| Talk about gene mutations causing molecular diseases. | Alteration of protein that doesn't have enzymatic activity (sickle cell anemia, HbA (normal) has 4 subunits, attached to hemes with one iron atom, HbS (sickled) decreases RBC life and changes it into sickle shaped, beta subunit is the affected one, substitution of GTG into GAG in number 6 aa of beta.) |
| Talk about genomic mutations. | AKA numerical, chromosome aberrations. Mainly a variation of the merged haploid cells forming the diploid cell, ranges from addition or loss of one or more chromosome sets bet not the complete set, called aneuploidy, loss in called monosomy, gain is called trisomy. Euploidy chromosomes having all sets changed three sets are called triploid, four tetrapoild.... |
| Talk about the monopoildy genomic mutation. | Having one set of chromosomes, lethal, distinct from hapoilds. |
| Talk about the polyploidy genomic mutation. | more than two multiples of chromosomes, triploidy happens when a problem in meosis I occurs of female fertilized by normal sperm. or vice versa, or fertilization of an egg by two sperms.
Tetraploidy is caused by failure of first zygotic mitosis where the replicated chromosomes stay in the same cell. |
| Talk about monosomy. | Autosomal aneuploidy, loss of one chromosome, may occur in gonosomes, like turner syndrome, autosomal ones are not tolerated and lethal, except animals. |
| Talk about trisomy. | Addition of extra chromosome, the only capable to survive is trisomy 21(Down syndrome), patau syndrome (trisomy 13) and Edwards syndrome (trisomy 18) but with severe malformations and early lethality. |
| Talk about sex chromosomes aneuploidy. | X inactivation and Y paucity cause them being more common than autosomal ones, usually do not lead to clinical signs or symptoms, triple X or double Y not clinical apparent, the only well defined is Klienfelter syndrome. |
| Talk about Kleinfilter syndrome. | More than one X, most often XXY, in addition to 44 autosomes, giving 47,XXY. Generally tall and long features, male genitalia, but sterile, 1 of every 660 males. XXXY XXYY and XXXXY are similar but more severe. |
| Talk about triple X syndrome. | Females, perfectly normal, in rare instances more X are found. |
| Talk about Jacob's syndrome. | 47,XYY males, long, subnormal intelligence and personality disorders |
| Talk about turner syndrome. | 45 chromosomes, 45,X. female genitalia, but sterile (rudimentary) short cognitive impairment, skin folds into neck, underdeveloped breasts. |
| Talk about non-disjunction in meiosis I and II. | Aneuploid variations are originated during gametogenesis, phenomenon called non-disjunction, where homologous chromosomes fail to disjoin, giving either two members of the affected chromosomes or non at all. Fertilizing them with normal haploid germ cell gives either a trisomy or monosomy, leading to a variety of aneuploid conditions.
Trisomy 21 frequently occurs during meiosis, during either anaphase I or II, about 75% during meiosis I. |
| How are Barr bodies present in aneuploid? | Such that only one X is active. |
| Talk about structural chromosome mutations | Variation in its composition, do not result from meiotic non-disjunction but from breakage followed by reconstitution and ligation of substantial portions of chromosomes, and rearrangement in which a chromosome segment is inverted and transferred to another chromosome making one merged chromosome, exchange and transfer is called translocation, They can be balanced or unbalanced depending on the gain or loss of genetic constitution of chromosome, Balanced are translocations and inversions, unbalanced are a gain or loss of constitution, translocations, deletion insertions duplications and rings. |
| Talk about inversions. | Balanced structural mutation, a chromosomal aberration is inverted 180 degree simple rearrangements, requires breaks at two ends of a chromosome, may be short or long, if centromere is a part of it its called Paracentric, if it is not its called pericentric. |
| Talk about translocations. | Transfer of a segment to another segment, three types, reciprocal (two way) and non-reciprocal, and Robertsonian (centric fusion between two acrocentric non-homologous chromosomes. |
| How does balanced structural mutation affect the phenotype? | They can result in an altered one, for example, reciprocal translocation results in involving 9 and 22 in one chromosome (philadelphia) chronic Leukemia. |
| What are the acrocentric chromosomes? | 13-14-15-21-22-Y |
| Talk about Robertsonian balanced translocation | common type of translocation, breaks extreme ends of acrocentric non-homologous chromosomes, these segments are lost, and the larger segments fuse at their centromeric region, producing a new large sube-metacentric or metacentric chromosome. |
| Talk about familial Down syndrome. | In some cases Down syndrome is familial (unlike the ones caused by non-disjunction of chromosome 21) These cases are most found when one of the parents is a carrier of Robertsonian translocation involving chromosome 21. Analysis reveals that there is a 14/21 translocation |
| Talk about unbalanced deletion structural chromosome abnormality. | When a chromosome is broken in one or two places and a portion is lost it is called deletion (deficiency), either near one end (terminal) or within interior part (intercalary) If a small part of the chromosome is deleted the organism might survive. |
| Talk about Cri Du Chat syndrome. | deletion of small segment of chromosome 5 partial monosomy, loss of small variable part of the p arm. |
| Talk about the unbalanced duplication. | increase in number of copies of the same chromosomal region. may arise as the result of an unequal crossing over during meiosis or through a replication error prior to meiosis. |
| Talk about ring chromosome. | arises when a chromosome breaks in two places and opposite arms are joined together to form a circular structure. Distal segments are lost. In rare cases telomeres at the end of chromosomes fuse without any loss, which results in normal phenotype, the bigger the loss the harder the phenotype change. |
| Talk about unbalanced translocations. | Gametogenesis of a carrier of a balanced translocation might lead to an unbalanced translocation. True for reciprocal and Robertsonian translocations. If we have a non-reciprocal translocation, only balanced segments are found in gametes. |
| Talk about gamete formation in case of structural chromosomal rearrangements. | When two chromosomes pair up in prophase I, they adopt a bivalent structure, chromosomes must pair up and recombine their genes in prophase I, so they rearrange their gene segments to be placed facing each other, which gives different configurations depending on type of rearrangement. |
| Talk about the Reciprocal translocation rearrangement. | Two cases (2 pairs and three pairs)
-Two pairs: Where two chromosomes are derivatives (subjected to reciprocal translocation) pairing results in tetravalent or cross like structure, which results in four potential meiotic products, pairing of 2 normal non-translocated chromosomes, a pair of 2 translocated but complementary chromosomes (balanced translocation) which segregates via alternate segregation, and 2 pairs of containing deleted and duplicated segments (unbalanced), meaning that aberrant gametes are not the result of only crossing over. |
| Talk about the case of three pairs of chromosomes for reciprocal translocation arrangements. | Derivates pair up in hexavalent star-like configuration Four cases:
-Robertsonian translocation: in this case, three chromosomes will pair up forming trivalent structure (trisomy)
-Deletion: formation of a DNA loop of deleted segments in the homologous chromosome for the normal one.
-Duplications: DNA loop in duplicated region.
-Inversions: only able to pair up by inversion loop. inversion heterozygous if only one is inverted. |
