instruction:
Given a question and a context passage, generate the answer having the word or phrase from the context passage. Here, the answer should be a shortest continous span from the passage.
question:
Context: Chronic myeloid leukemia (CML) is genetically characterized by the presence of the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL gene fusion on the derivative chromosome 22 called the Philadelphia (Ph) chromosome. In 2-10% of the cases, this chimeric gene is generated by variant rearrangements, involving 9q34, 22q11, and one or several other genomic regions. All chromosomes have been described as participating in these variants, but there is a marked breakpoint clustering to chromosome bands 1p36, 3p21, 5q13, 6p21, 9q22, 11q13, 12p13, 17p13, 17q21, 17q25, 19q13, 21q22, 22q12, and 22q13. Despite their genetically complex nature, available data indicate that variant rearrangements do not confer any specific phenotypic or prognostic impact as compared to CML with a standard Ph chromosome. In most instances, the t(9;22), or a variant thereof, is the sole chromosomal anomaly during the chronic phase (CP) of the disease, whereas additional genetic changes are demonstrable in 60-80% of cases in blast crisis (BC). The secondary chromosomal aberrations are clearly nonrandom, with the most common chromosomal abnormalities being +8 (34% of cases with additional changes), +Ph (30%), i(17q) (20%), +19 (13%), -Y (8% of males), +21 (7%), +17 (5%), and monosomy 7 (5%). We suggest that all these aberrations, occurring in >5% of CML with secondary changes, should be denoted major route abnormalities. Chromosome segments often involved in structural rearrangements include 1q, 3q21, 3q26, 7p, 9p, 11q23, 12p13, 13q11-14, 17p11, 17q10, 21q22, and 22q10. No clear-cut differences as regards type and prevalence of additional aberrations seem to exist between CML with standard t(9;22) and CML with variants, except for slightly lower frequencies of the most common changes in the latter group. The temporal order of the secondary changes varies, but the preferred pathway appears to start with i(17q), followed by +8 and +Ph, and then +19. Molecular genetic abnormalities preceding, or occurring during, BC include overexpression of the BCR/ABL transcript, upregulation of the EVI1 gene, increased telomerase activity, and mutations of the tumor suppressor genes RB1, TP53, and CDKN2A. The cytogenetic evolution patterns vary significantly in relation to treatment given during CP. For example, +8 is more common after busulfan than hydroxyurea therapy, and the secondary changes seen after interferon-alpha treatment or bone marrow transplantation are often unusual, seemingly random, and occasionally transient. Apart from the strong phenotypic impact of addition of acute myeloid leukemia/myelodysplasia-associated translocations and inversions, such as inv(3)(q21q26), t(3;21)(q26;q22), and t(15;17)(q22;q12-21), in CML BC, only a few significant differences between myeloid and lymphoid BC are discerned, with i(17q) and TP53 mutations being more common in myeloid BC and monosomy 7, hypodiploidy, and CDKN2A deletions being more frequent in lymphoid BC. The prognostic significance of the secondary genetic changes is not uniform, although abnormalities involving chromosome 17, e.g., i(17q), have repeatedly been shown to be ominous. However, the clinical impact of additional cytogenetic and molecular genetic aberrations is most likely modified by the treatment modalities used.
Question: Which gene fusion is the result of the "philadelphia translocation" or the "philadelphia chromosome" mutation?
answer:
the bcr/abl gene fusion

question:
Context: From the outside, the skin looks plain and simple, as you can see in Figure 16.5. But at a cellular level, theres nothing plain or simple about it. A single square inch of skin contains about 20 blood vessels, hundreds of sweat glands, and more than a thousand nerve endings. It also contains tens of thousands of pigment-producing cells. Clearly, there is much more to skin than meets the eye! For a dramatic introduction to the skin, watch this video: MEDIA Click image to the left or use the URL below. URL: The skin is only about 2 mm thick, or about as thick as the cover of a book. Although it is very thin, it consists of two distinct layers, called the epidermis and the dermis. You can see both layers and some of their structures in Figure 16.6. Refer to the figure as you read about the epidermis and dermis below. The epidermis is the outer layer of skin. It consists almost entirely of epithelial cells. There are no blood vessels, nerve endings, or glands in this skin layer. Nonetheless, this layer of skin is very active. It is constantly being renewed. How does this happen? 1. The cells at the bottom of the epidermis are always dividing by mitosis to form new cells. 2. The new cells gradually move up through the epidermis toward the surface of the body. As they move, they produce the tough, fibrous protein called keratin. 3. By the time the cells reach the surface, they have filled with keratin and died. On the surface, the dead cells form a protective, waterproof layer. 4. Dead cells are gradually shed from the surface of the epidermis. As they are shed, they are replaced by other dead cells that move up from below. The epidermis also contains cells called melanocytes. You can see a melanocyte in Figure 16.7. Melanocytes produce melanin. Melanin is a brown pigment that gives skin much of its color. Everyones skin has about the same number of melanocytes per square inch. However, the melanocytes of people with darker skin produce more melanin. The amount of melanin that is produced depends partly on your genes and partly on how much ultraviolet light strikes your skin. The more light you get, the more melanin your melanocytes produce. This explains why skin tans when its exposed to sunlight. The dermis is the inner layer of skin. It is made of tough connective tissue. The dermis is attached to the epidermis by fibers made of the protein collagen. The dermis is where most skin structures are located. Look again at Figure pain, pressure, and temperature. If you cut your skin and it bleeds, the cut has penetrated the dermis and damaged a blood vessel. The cut probably hurts as well because of the nerve endings in this skin layer. The dermis also contains hair follicles and two types of glands. You can see some of these structures in Figure 16.8. Hair follicles are structures where hairs originate. Each hair grows out of a follicle, passes up through the epidermis, and extends above the skin surface. Sebaceous glands are commonly called oil glands. They produce an oily substance called sebum. Sebum is secreted into hair follicles. Then it makes its way along the hair shaft to the surface of the skin. Sebum waterproofs the hair and skin and helps prevent them from drying out. Sweat glands produce the salty fluid known as sweat. Sweat contains excess water, salts, and other waste products. Each sweat gland has a duct that passes through the epidermis. Sweat travels from the gland through the duct and out through a pore on the surface of the skin. You couldnt survive without your skin. It has many important functions. In several ways, it helps maintain homeostasis. The main function of the skin is controlling what enters and leaves the body. It prevents the loss of too much water from the body. It also prevents bacteria and other microorganisms from entering the body. Melanin in the epidermis absorbs ultraviolet light. This prevents the light from reaching and damaging the dermis. The skin helps maintain a constant body temperature. It
Question: __oily substance secreted by glands in the skin
answer:
sebum

question:
Context: In recent years, we have seen remarkable progress in our understanding of the disease mechanism underlying facioscapulohumeral muscular dystrophy (FSHD). The purpose of this review is to provide a comprehensive overview of our current understanding of the disease mechanism and to discuss the observations supporting the possibility of a developmental defect in this disorder. In the majority of cases, FSHD is caused by contraction of the D4Z4 repeat array (FSHD1). This results in local chromatin relaxation and stable expression of the DUX4 retrogene in skeletal muscle, but only when a polymorphic DUX4 polyadenylation signal is present. In some cases (FSHD2), D4Z4 chromatin relaxation and stable DUX4 expression occur in the absence of D4Z4 array contraction. DUX4 is a germline transcription factor and its expression in skeletal muscle leads to activation of early stem cell and germline programs and transcriptional activation of retroelements. Recent studies have provided a plausible disease mechanism for FSHD in which FSHD results from inappropriate expression of the germline transcription factor DUX4. The genes regulated by DUX4 suggest several mechanisms of muscle damage, and provide potential biomarkers and therapeutic targets that should be investigated in future studies.
Question: Which disease is associated with the ectopic expression of the protein encoded by the gene DUX4?
answer:
fshd