Generally speaking, which of the following would most severely affect the protein coded for by a gene? -a base substitution at the beginning of the gene -a base substitution at the end of the gene -a frameshift deletion at the beginning of the gene -a frameshift deletion at the end of the gene

The answer is a frameshift deletion at the beginning of the gene.

The frameshift deletion means that due to the deletion, the reading frame will be changed. Because of this, changed mRNA will be synthesized and translated into altered protein. It is known that codon is a triplet (a set of three nucleotides), that code for certain amino acid. The earlier in the sequence the deletion occurs, the protein will be more severely affected.
For example, if codons on RNA are THE BIG BAD DOG and the frameshift deletion happens on the first triplet (earlier in the sequence), the changed sequence will be  TEB IGB ADD OG. If the frameshift deletion happens on the third triplet (later in the sequence), the changed sequence will be THE BIG ADD OG. This way, if the frameshift deletion occurs at the beginning of the gene, the more codons will be changed and in turn, they will code different amino acids.

Then it is june the conclusion to the second sentence is just restating "if it is june then it is summer"