Page 65 - Genetics_From_Genes_to_Genomes_6th_FULL_Part3

Solved Problems 359

each of us has our own human genome that is closely re- differences between the genomes of many individuals so
lated to that of all other humans but is also distinct and we can understand the genetic basis of phenotypic varia-
unique. It is the differences between the genomes of indi- tion; for example, finding the nucleotide differences re-
viduals that cause each of us to possess our own distinct sponsible for far-ranging and varied effects on human
and unique phenotype. health. In Chapter 11, we describe how geneticists can now
The sequence and even the annotation of one human look at the genomes of many individuals to track genetic
genome is only the beginning. The human RefSeq provides variation and to identify those differences in DNA se-
a reference mark toward identifying and analyzing the quence that underlie important traits.

SOLVED PROBLEMS

I. The following figure shows a screen shot from the b. The arrows within the introns of the gene show that
UCSC Genome Browser, focusing on a region of the hu- the direction of transcription is from the telomere of
man genome encoding a gene called MFAP3L. (Note: 4q toward the centromere of chromosome 4.
hg38 refers to version 38 of the human genome RefSeq.)
If you do not remember how the browser represents the c. The data indicate four alternatively spliced forms of
genome, refer to the key at the bottom of Fig. 10.3. the mRNA. In the following parts, we list these as A
to D from top to bottom.
d. The data suggest two promoters. One is roughly at po-
sition 170,037,000 and allows the transcription of a
primary RNA alternatively spliced to produce
mRNAs B and D. The other is roughly at position
170,013,000 and leads to the transcription of a pri-
mary RNA alternatively spliced to generate mRNAs
A and C.
Source: University of California Genome Project, https://genome.ucsc.edu
e. The data indicate that the MFAP3 gene can encode
a. Describe in approximate terms the genomic loca- two different but closely related proteins. mRNAs A,
tion of MFAP3L. B, and C all encode the same protein; mRNA D a
b. Is the gene transcribed in the direction from the slightly larger protein that includes at its N terminus
centromere-to-telomere or from the telomere-to- additional amino acids not found in the other protein.
centromere? Otherwise these two proteins appear to be the same.
c. How many alternative splice forms of MFAP3L The ORF that encodes the A B C protein form is
mRNA are indicated by the data? about 880 bp long (a rough estimate); this corre-
d. How many different promoters for MFAP3L are sponds to about (880/3 = 293 amino acids). The D
protein is about 50 amino acids longer.
suggested by the data?
e. How many different proteins does the MFAP3L II. Two parents from Southeast Asia have a stillborn
gene appear to encode? Which alternatively spliced child with a lethal condition called hydrops fetalis.
forms of the mRNA encode which proteins? Do the The parents themselves have α-thalassemia trait (mild
different forms vary at their N termini, their C ter- anemia) and microcystosis (abnormally small red
mini, or somewhere in the middle? Estimate how blood cells). Remember that humans have two essen-
many amino acids each of these proteins contains. tially identical Hbα genes (Hbα1 and Hbα2) and that
the genes are autosomal, so normal humans have two
Answer copies of each (Fig. 10.21).
a. The gene is located on the long (q) arm of human a. If this couple has many conceptions, what percent-
chromosome 4; this position is denoted by the thin red age of these conceptions is expected to result in
vertical line on the chromosome representation (an hydrops fetalis?
idiogram) at the top of the figure. This location (in a b. Two other parents, who come from North Africa,
band called 4q33) is roughly 170 million bp from the also both have α-thalassemia trait, but a genetics
telomere of the small arm of chromosome 4 (from counselor told them that none of their conceptions
where the numbering begins); the total length of this would result in hydrops fetalis. Explain how the
chromosome is about 190 million bp. genetic counselor’s advice could be correct.