Question

3· The figure below shows the structure of the human version of the tinman gene (NKX2-5 is the vertebrate homologue of tinman). It also shows the mutations found in the affected families and compares the homoebox sequence of the human gene to other similar genes. Figure 3 Structure of the human NKX2-5gene, positions of mutations, and sequence comparison to related gens: ATG TAG The 17Met ain19 Ter GAntp Structure of the human NKX2-5gene positions of mutations, and sequence comparison to related genes. (A)NKX2-5is encoded by two exons (open rectangles) separated by a 1.5-kb intron. Primer sequences are denoted and provided in (14). Mutations Gin17Oter and Thr178Metater sequencesin helix 2 of the homeodomain (dark hatching). The Gin198ter mutation terminates translation just after helix 3, thereby deleting the COOH-terminal Nk domain (clear hatching). (B) Comparison of normal and mutant NKX2-5sequences (21)with members and related genes:thyroid nuclearfactor-1TTF-1), tinman bagpipe, and antennapedia (Antp) (13,16). Gene names are prefxed with a speciesabbreviation in lower case: h, human, m, mouse: x, Xenopuslaevis e, chicken; and d Drosophila Dots denote identity, letters denote amino acid differences. Asterisks indicate termination signals. The Thr178Metdefect alters a residue that is highly conserved in related genes. Three a helices within the homeodomain are indicated below the sequences n sequences in other NK gene famly Science Pubished by AAAS Jean Jacques Schott et al. Science 1998,281:108-111 a. (8 points) How many introns and exons are there in the human NKX2-5 gene? b. (9 points) What is Gln170Ter? part of the tinman gene are each of these found in? What is Thr178Met? What is Gln198Ter? What

Answer 1

a. In the human NKX2-5 gene which is responsible for the development of heart contain 2 exons and 1 intron.

b. Gln170Ter: it is a nonsense mutation in the Homeodomain.

Thr178Met: it is a missense mutation within the Homeodomain.

Gln198: it is a truncation mutation occuring at the COOH terminal of homeodomain.

All these found in the exon part of the tinnman gene in homeodomain.