Question
uesti on 1 state of our knowledge concerning Syndrome X. All of w summarizes the curren ents of the stud rome has been fabricated so as not to deprive our e data to form e responses to the questions that follow the Entell summa e actual name of synd ual rom utilizing a) Syndi gene s from a defect at one genetic locus and patients with terior c disorder that resul embryonic development. These effects include of effects that occur dun disease known as glaucom in 50% of d the the eye a head and (which causes d underdevelop teeth. One of the pedigrees face ped ance of the disorder is found below. sord er manife malfo es rome X used ermine the mode of b) Fam es displaying the di amily. From such to each were examined for linkage of the disease locus to a site unique scientists were ble to report linkage of the gene that is defective in the a sease es er to chi of the gene that is defective ill use the term "gene x" to designate the normal form point on we w rome X) c) Invest n ors used methodology for isolating a cDNA clone coding for a one knows nothing a eg a cDNA about the function of the protein encoded by the gene and has no for y library, and ultimately isolated a length cDNA clone coding for the normal gene isolated a human genomic clone coding for gene x Subsequent d) The cDNA clone as well as parts of the genomic clone were sequenced. The results are shown in Fig. 1 c) since nothing was known about the or function of the prote encoded by gene x, scientists deduced its amino acid stud es. The sequence from the cDNA nucleotide sequence of gene x and used it for further of accuracy, deduced amino acid sequence was analyzed via software capable of predicting with some degree a second structure of a protein not the complete tertiary structure) and the presence o helix-turn-helix ary was revealed to utant gene x isolated from members of 10 different families diagnosed with Syndrome X were analyzed identify th mutations therein, Or family showed the following number was e nged m a G to an A ne Fig 1. The other nine families showed other distinct mutations fro as shown in g) t is often helpful when studying human genetic disorders to have a mouse model of the disease as well as mouse cDNA clone for the gene und er study. For this reason, scientists isolated a mouse cDNA whos deduced amino acid sequence showed a 91% similarity to the deduced amino acid sequence for human ge Utilizing all of the data presented n conjunction with the many concepts that you have learned this semester answer the questions that follow 1. (.5 pts) Using th pedigree, state th given e probable mode of inheritance of Syndrome X. 2. (5 pts) Why did the researchers choose to clone gene via positional cloning rather than via the less (Do not our time trying to figure laborious and more direct approach of screening a cDN out the methodology of positional cloning. You be gnorant of this methodology but easily answer the question with the information given.)
Explanation / Answer
1. Since it is a mutation on chromosome 4, we know that it is an autosomal inheritance.
This inheritance may be dominant i.e. heterozygous dominant (say Aa) and homozygous dominant (say AA) will be affected; whereas homozygous recessive (say aa) will not be affected. Conversely,this inheritance may be recessive i.e. heterozygous dominant (say Aa) and homozygous dominant (say AA) will not be affected; whereas homozygous recessive (say aa) will be affected.
From the pedigree analysis, we can see that the inheritance follows the dominant pattern.
The parents are heterozygous dominant (affected) and homozygous recessive (unaffected). This gives rise to 50% of the progeny being affected while the other 50% is unaffected. (F1 has 1:1 ratio)
In the subsequent filial we see that 5 of the 8 progenies are affected. (F2 has nearly 2:1 ratio)
So from the given data we can deduce the inheritance to be autosomal dominant.
2. A cDNA library is is formed using a mature mRNA that gives only the functional coding region. Since it is given the we don't know anything about the function of the protein coded and therefore have no probe to use for screening in the cDNA library; it is much more useful to use positional cloning.
