Disorders Inheritance Patterns - Essay Example

Medical Genetics: Pedigree and Disorders Inheritance Patterns Medical Genetics: Pedigree and Disorders Inheritance Patterns 1. Pedigree Figure 1 Pedigree of a Dutch family showing deafness inheritance pattern 2. It is a non-Mendelian inheritance multifactorial inheritance pattern because a single parent can transmit the disorder to the child. In the pedigree, the fourth generation exhibits no signs of either IGT/IFG or DM. There are descriptions of diabetes in families resulting due to mutations on the mitochondrial genes. Offspring with mothers who are diabetic often have milder hypertension prevalence. A couple of healthy fathers, but an infected mother shows result of decedents that exhibit symptoms of impaired fasting glucose. A couple of a male having IFG and a healthy female has healthy children exhibiting no signs of Diabetes mellitus or IGG. 3. This is a non-syndromic deafness trait, which has a gene locus called DFNA12. 4. Giving the allele symbol M (dominant allele), m (recessive allele) the proband genotype is MM and the husband’s genotype is mm. If II: 2 is heterozygous, her genotype will be Mm. III: 1 will be heterozygous or homozygous with equal possibilities. This because the genes cross and combines to produce a child that has a genotype of either Mm, Mm, mm or mm as shown in table 1. Table 1 Punnett square M m M MM Mm m Mm mm 5. The risk of a boy or a girl to express the trait is 50%. 6. There is a 100% risk of the II: 1’s next child inheriting the trait. This is because when the parents are crossed, the resulting genotypes will be Mm as shown in table 2. Table 2 Punnett table m m M Mm Mm M Mm Mm . 7. It is not possible because II.12 has a possibility 75% possibility of having a healthy girl and 25% of having the one with the trait. The genotypes of the III.12 daughter either are Mm, mm, mm, or mm. 8. This is a transverse reaction. The amino acids change due TTC trinucleotide deletion in their codon. This is a non-conservative substitution reaction whereby Gly 148 (GGG) changes to Arg148 (AGG). 9. Deamination results from DNA replication that is by unequal strand crossover events. Repetitive sequences at the misalignments cause deletions and nucleotide addition to the molecules of DNA. 10. Yes, gene mutation leads to ether deletions or insertions caused by the uncertainties during the chromosomal crossover due to meiosis. This causes misalignment of homologous chromosomes leading to a different structure of the DNA. Part 2: Linkage and positional cloning (A) 1. This pattern of inheritance is X- linked Autosomal-dominant hearing-impairment. 2. Gametes genotypes produced by II.1 and II.2 are heterozygous by analyzing the possible genotypes the parent will produce as shown below; 3. The frequency of homozygous and heterozygous gametes expected from II.2 is computed using Punnett table 3 with the information on the pedigree. Consequently, the two genotypes have equal frequency of occurrence of 50%. Table 3, Punnett Table X x X XX Xx x Xx xx 4. Assuming the recessive allele xx, then the table is computed as shown below. x x x xx xx x xx xx Consequently, the genotype for the children of would be homozygous with recessive allele 5. Typically, it is a Mendelian inheritance. This is because offspring with a dominant allele from either of the parents has the trait, and dominant allele dominates the recessive allele. The pedigree indicates phenotypic traits that show co-dominance of the dominant allele. Part 2: (B) i) II: 2 inherited alleles [212122] the deceased mother I.1. ii) The deafness trait was inherited from the deceased mother I.1. iii) i) and ii) shows that allele 212122 is linked to the deafness trait iv) The trait segregation markers are DS3-1569, -3554, -1569 and -1292 v) III.5 inherited the trait from parent II: 2. vi) The recombination between the trait locus and alleles DS3- 3554 and -1569 occurred for three children: III. 1, III: 7, and III: 10. vii) Assuming No. of full linkage recombinant in the family, according to the pedigree=3. The no. of total progeny is 9 but one is exceptional hence the no. on non-recombinant offspring is 8. Consequently, probability of observing children of II.2 genotype is given by 0/2=infinity. Parental probability =hence linkage genotype probability (very small), which is the probability of sequence with linkage ()=0 viii) In independent linkage, the probability multiplies for each linkage probability is given by ¼ (0.25) because all four possible genotypes are equally probable. Hence probability of birth sequence with no linkage = =0.0000153 ix) Newton E. Morton’s formulae calculate the LOD score as, =. This indicates that complete linkage is not possible (i.e.) there is exclusion between the trait and the marker. x) Morgan’s map function ( : Where, is the recombination frequency between A and C, is the recombination frequency existing in A and B, = the recombination frequency taking place between B and C, and =Coefficient of coincidence) calculating for map distance gives, xi) Number of Genes expected =. xii) U2-SURP has a suitable sequence for position cloning hence the best candidate. xiii) Genetic association database xiv) A haplotype is a set of genes inherited from a single parent. It is problematic because of associated diseases that can spread to the population. xv) Polymorphism phenomenon and contributes the deafness trait. Part 3: Chromosome Abnormalities 1. DNA architectural features 2. Balanced Chromosome translocation readjust non-homologous chromosomes hence no genotype formation. 3. Robertsonian translocation is a collective form of chromosomal readjustment that occurs in the13, 14, 15, 21, and 22 acrocentric chromosome pairs. 4. The six embryos are calculated as follows; , , , ; 45,, XXX. 4% of mosaic cases were XY conceptuses who are: 45,, XY. Triple X has an incidence of approximately 1/1000 female births. 47-XXX are usually fertile and are likely to suffer from syndromes due to chromosomal abnormalities due to Biotinidase deficiency. 5. Prophase oocytes lack a pre-defined polarity. 6. Cytological technique and prenatal diagnosis are good cytological detection methods. Part 4: Congenital Disorder: sickle cell anemia Sickle cell anemia has an autosomal recessive inheritance pattern caused by defect of the HBB ; Haemoglobin, beta gene, which is a protein coding gene, and involves a transition mutation as shown in fig.2. The frequency of the trait among the population is high with a number of millions in the world and occurs in 1out of 500 African American offspring. In every 1400 Hispanic-American births, there are 100 infected. Estimated 2 million Americans have the trait while in Africa, 1 in every 12 individual carry the trait (Jennifer 2005). The chromosome location is 11-NC_000011.9. The GAA or GAG gene coding of amino acid in sickle cell anemia trait is changed to valine due to a single-phase change. This cause the allele change mutation in beta globin gene. Figure 2 Transition Mutation mechanism and gene coding of Haemoglobin HBB in sickle cell anemia disorder Protein structure of is shown as below; Figure 3 a) The Crystal Structure of Human Deoxy- Haemoglobin b) model of two clubbing Hb S hemoglobin molecules as viewed in the protein bank. The effect of transition is shown as below, There is a different pattern of symptoms related to sickle cell anemia. Some patients experience mild symptoms while others may have severe symptoms. Hand –foot syndrome appears first due to blocked blood vessels. Other symptoms include; fatigue, paleness, and breathing difficulties, unpredictable pain occurring in body parts and joints, eye problems, yellowing of skin and eyes, and stunted growth, and delayed puberty caused by insufficient red blood cells. Sickle cell anemia has no cure, but measures are taken to control complication associated to the trait. These measures include; administration of oral antibiotics that prevent bacterial infection. A blood transfusion is an effective disorder treatment by increasing the number of red blood cells. References Laura, G. & Scott, M., 2010. Essentials of Medical Genetics for Health Professionals. United State, U.S.: Jones & Bartlett Learning. Ensembl, 2000, European Bioinformatics Institute, United Kingdom, accessed 8 February 2013, . Joanna, R. F. & Stephen D. P., 2011. Molecular Ecology. Canada :John Wiley & Sons. CIBA, F. S., 2009. Aetiology of Diabetes Mellitus and its Complications. Canada: John Wiley & Sons. Jennifer, B., 2005. U.S. U.S. Department of Energy Biological and Environmental Research program, U.S., accessed 8 February 2013, . Ralph, W. & Harlan, M., 2012. Pediatric otolaryngology. New York, NY: Thieme Ondrej, S, Frantisek, L. & Lucie, Š. 2005. Current genetics: genetics and genomics, e-book, accessed 8 February2013, Strachan, T. & Andrew P. R., 2004. Human Molecular Genetics. New York, N Y: Garland Science. Progeny, 1996, Progeny Software, LLC, accessed on 8 February 2013, . Pedigree chart designer, Center for Genomics and Transcriptomics, Germany, accessed 8 February 2013, . PubMed Health, 2012, National center for Biotechnology information, United States, accessed 8 February 2013, . Emil G, I. M, & Robert C., 2006. Theoretical Aspects of Pedigree Analysis. Israel: Ramot-tel Aviv University. Protein data bank, 2013, NSF, accessed on 8 February, . 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